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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 10-K
(Mark One)
☒
ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended December 31, 2024
OR
☐
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the transition period from to
Commission File Number 001-34620
IRONWOOD PHARMACEUTICALS, INC.
(Exact name of registrant as specified in its charter)
Delaware
(State or other jurisdiction of
incorporation or organization)
04-3404176
(I.R.S. Employer
Identification Number)
100 Summer Street, Suite 2300
Boston, Massachusetts
(Address of Principal Executive Offices)
02110
(Zip Code)
(617) 621-7722
(Registrant’s telephone number, including area code)
Securities registered pursuant to Section 12(b) of the Act:
Title of each class
Trading Symbol(s)
Name of each exchange on which registered
Class A Common Stock, $0.001 par value
IRWD
Nasdaq Global Select Market
Securities registered pursuant to Section 12(g) of the Act: None
Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No ☒
Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or 15(d) of the Act. Yes ☐ No ☒
Indicate by check mark whether the registrant: (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the
preceding 12 months (or for such shorter period that the registrant was required to file such reports) and (2) has been subject to such filing requirements for the past 90 days. Yes ☒
No ☐
Indicate by check mark whether the Registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T
(§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the Registrant was required to submit such files). Yes ☒ No ☐
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth
company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.
Large accelerated filer ☒
Accelerated filer ☐
Non-accelerated filer ☐
Smaller reporting company ☐
Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised
financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial
reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. ☒
If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the
correction of an error to previously issued financial statements. ☐
Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the
registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒
Aggregate market value of voting stock held by non-affiliates of the Registrant as of June 28, 2024: $916,974,495
As of February 28, 2025, there were 161,809,432 shares of Class A Common Stock outstanding.
DOCUMENTS INCORPORATED BY REFERENCE:
Portions of the definitive proxy statement to be filed for our 2025 Annual Meeting of Stockholders are incorporated by reference into Part III of this report.
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1
NOTE REGARDING FORWARD-LOOKING STATEMENTS
This Annual Report on Form 10-K, including the sections titled “Business,” “Risk Factors” and “Management’s
Discussion and Analysis of Financial Condition and Results of Operations”, contains forward-looking statements. All
statements contained in this Annual Report on Form 10-K other than statements of historical fact are forward-looking
statements, within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include
statements regarding our future financial position, business strategy, budgets, projected costs, plans and objectives of
management for future operations. The words “may,” “continue,” “estimate,” “intend,” “plan,” “will,” “believe,” “project,”
“expect,” “seek,” “anticipate,” “could,” “should,” “target,” “goal,” “potential” and similar expressions may identify forward-
looking statements, but the absence of these words does not necessarily mean that a statement is not forward-looking. These
forward-looking statements include, among other things, statements about:
●
the demand and market potential for our products in the countries where they are approved for marketing, as
well as the revenues therefrom;
●
the timing, investment and associated activities involved in commercializing LINZESS® by us and AbbVie Inc.
in the U.S.;
●
the commercialization of CONSTELLA® in Europe and LINZESS in Japan and China, as well as our
expectations regarding revenue generated from our partners;
●
the timing, investment and associated activities involved in developing, obtaining regulatory approval for,
launching, and commercializing our products and product candidates, such as apraglutide, by us and our partners
worldwide;
●
our ability and the ability of our partners to secure and maintain adequate reimbursement for our products;
●
our ability and the ability of our partners and third parties to manufacture and distribute sufficient amounts of
linaclotide active pharmaceutical ingredient, finished drug product and finished goods, as applicable, on a
commercial scale;
●
our expectations regarding U.S. and foreign regulatory requirements for our products and our product
candidates, such as apraglutide, including our post-approval development and regulatory requirements;
●
the ability of apraglutide and our other product candidates to meet existing or future regulatory standards;
●
the safety profile and related adverse events of our products and our product candidates;
●
the therapeutic benefits and effectiveness of our products and our product candidates and the potential
indications and market opportunities therefor;
●
our ability and the ability of our partners to obtain and maintain intellectual property protection for our products
and our product candidates and the strength thereof, as well as Abbreviated New Drug Applications filed by
generic drug manufacturers and potential U.S. Food and Drug Administration approval thereof, and associated
patent infringement suits that we have filed or may file, or other action that we may take against such
companies, and the timing and resolution thereof;
●
our ability and the ability of our partners to perform our respective obligations under our collaboration, license
and other agreements, and our ability to achieve milestone and other payments under such agreements;
●
our plans with respect to the development, manufacture or sale of our product candidates and the associated
timing thereof, including the design and results of pre-clinical studies and clinical trials;
●
the in-licensing or acquisition of externally discovered businesses, products or technologies, or other strategic
transactions, as well as partnering arrangements, including the timing of potential clinical
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2
development and regulatory milestones and expectations relating to the completion of, or the realization of the
expected benefits from, such transactions;
●
our expectations as to future financial performance, revenues, expense levels, payments, cash flows,
profitability, tax obligations, capital raising and liquidity sources, and real estate needs, as well as the timing and
drivers thereof, and internal control over financial reporting;
●
our ability to repay our outstanding indebtedness when due, or redeem or repurchase all or a portion of such
debt, as well as the potential benefits of the capped call transactions described herein;
●
asset impairments, and the drivers thereof, and purchase commitments;
●
the status of government regulation in the life sciences industry, particularly with respect to healthcare reform
and drug pricing; trends and challenges in our potential markets; trends and challenges in our potential markets;
and our ability to attract, motivate and retain key personnel; and
●
other factors discussed elsewhere in this Annual Report on Form 10-K.
Any or all of our forward-looking statements in this Annual Report on Form 10-K may turn out to be inaccurate.
These forward-looking statements may be affected by inaccurate assumptions or by known or unknown risks and
uncertainties, including the risks, uncertainties and assumptions identified under the heading “Risk Factors” in this Annual
Report on Form 10-K. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances
discussed in this Annual Report on Form 10-K may not occur as contemplated, and actual results could differ materially from
those anticipated or implied by the forward-looking statements.
You should not unduly rely on these forward-looking statements, which speak only as of the date of this Annual
Report on Form 10-K. Unless required by law, we undertake no obligation to publicly update or revise any forward-looking
statements to reflect new information or future events or otherwise. You should, however, review the factors and risks we
describe in the reports we will file from time to time with the U.S. Securities and Exchange Commission, or the SEC, after the
date of this Annual Report on Form 10-K.
Summary of Risks Associated with our Business
Our business is subject to a number of risks, which are discussed more fully under the heading “Risk Factors” in this
Annual Report on Form 10-K. These risks include the following:
●
We are highly dependent on the commercial success of LINZESS® (linaclotide) in the United States, or the
U.S., for the foreseeable future.
●
We are subject to uncertainty relating to pricing and reimbursement policies in the U.S., including recent and
future healthcare reform measures, which, if not favorable for our products, could hinder or prevent our
products’ commercial success.
●
Healthcare reform and other governmental and private payor initiatives may have an adverse effect upon,
and could prevent, our products’ or product candidates’ commercial success.
●
We cannot give any assurance that apraglutide will receive regulatory approval, which is necessary before it
can be commercialized.
●
The regulatory approval processes in the U.S., in the E.U. and in other foreign jurisdictions are onerous,
lengthy, time consuming, expensive and inherently unpredictable. If we are ultimately unable to obtain
regulatory approval for apraglutide or our other product candidates, our business will be harmed.
●
Our failure to successfully develop and commercialize additional product candidates or approved products
would impair our ability to grow and/or adversely affect our business.
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3
●
Delays in the completion of clinical testing of any of our products or product candidates could result in
increased costs and delay or limit our ability to generate revenues.
●
We must work effectively and collaboratively with AbbVie Inc. (together with its affiliates) to market and
sell LINZESS in the U.S., and must adapt our commercial model and market strategy to the evolving
landscape for LINZESS to achieve its maximum commercial potential.
●
We face competition and new products may emerge that provide different or better alternatives for treatment
of the conditions that our products are approved to treat.
●
Our products or product candidates may cause undesirable side effects or have other properties that could
delay or prevent their development, create unpredictable clinical trial results, impact its regulatory approval or
limit their commercial potential.
●
Even though LINZESS is approved by the U.S. Food and Drug Administration for use in adult and certain
pediatric patients, post-approval development and regulatory requirements still remain, which may present
additional challenges.
●
If we are unable to execute on our strategy to in-license or acquire externally developed products or product
candidates, or engage in other transactions with value creation potential, our business and prospects would be
materially adversely affected.
●
We may be unable to maintain the benefits associated with orphan drug designation, including market
exclusivity, which may harm our business.
●
If we are unable to successfully partner with other companies to develop and commercialize products and/or
product candidates, our ability to grow would be impaired and our business would be adversely affected.
●
We may need additional funding and may be unable to raise capital when needed, which could cause us to
delay, reduce or eliminate our corporate or product development or commercialization efforts.
●
Our indebtedness could adversely affect our financial condition or restrict our future operations.
●
We have identified material weaknesses in our internal control over financial reporting. If we are not able to
remediate these material weaknesses, it could have an adverse effect on our business and financial results, and
our ability to meet our reporting obligations could be negatively affected.
●
Our quarterly and annual operating results may fluctuate significantly.
●
Limitations on our ability to obtain patent protection and/or the patent rights relating to our products and our
product candidates may limit our ability to prevent third parties from competing against us.
NOTE REGARDING TRADEMARKS
LINZESS® and CONSTELLA® are trademarks of Ironwood Pharmaceuticals, Inc. Any other trademarks referred to
in this Annual Report on Form 10-K are the property of their respective owners. All rights reserved.
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4
TABLE OF CONTENTS
Page
PART I
Item 1.
Business
5
Item 1A.
Risk Factors
26
Item 1B.
Unresolved Staff Comments
61
Item 1C.
Cybersecurity
62
Item 2.
Properties
62
Item 3.
Legal Proceedings
62
Item 4.
Mine Safety Disclosures
63
PART II
Item 5.
Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of
Equity Securities
64
Item 6.
[Reserved]
65
Item 7.
Management’s Discussion and Analysis of Financial Condition and Results of Operations
66
Item 7A.
Quantitative and Qualitative Disclosures about Market Risk
80
Item 8.
Financial Statements and Supplementary Data
81
Item 9.
Changes in and Disagreements With Accountants on Accounting and Financial Disclosure
81
Item 9A.
Controls and Procedures
81
Item 9B.
Other Information
87
Item 9C.
Disclosure Regarding Foreign Jurisdictions that Prevent Inspections
87
PART III
Item 10.
Directors, Executive Officers and Corporate Governance
87
Item 11.
Executive Compensation
87
Item 12.
Security Ownership of Certain Beneficial Owners and Management and Related Stockholder
Matters
87
Item 13.
Certain Relationships and Related Transactions, and Director Independence
88
Item 14.
Principal Accountant Fees and Services
88
PART IV
Item 15.
Exhibits and Financial Statement Schedules
89
Item 16.
Form 10-K Summary
95
Signatures
96
Index to Consolidated Financial Statements
F-1
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5
PART I
Item 1. Business
Our Company
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.
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. (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.
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,
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development and commercialization of linaclotide, as well as to the research and development of apraglutide and our other
product candidates.
Drug development involves a high degree of risk and investment, and the status, timing and scope of our
development programs are subject to change. Important factors that could adversely affect our drug development efforts are
discussed under the heading “Risk Factors” in this Annual Report on Form 10-K.
Performance Against 2024 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
●
We recognized $340.4 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. 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.
Deliver sustained profits and cash flow
●
We generated $103.5 million in cash from operations during the year ended December 31, 2024, ending the year
with $88.6 million in cash and cash equivalents.
Linaclotide
IBS-C and CIC are chronic, functional GI disorders that afflict millions of sufferers worldwide. As many as
11.5 million adults suffer from IBS-C and as many as 28.5 million adults suffer from CIC in the U.S., based on Rome II
criteria from the Lieberman GI Patient Landscape Survey performed in 2010, or the Lieberman Survey. Symptoms of IBS-C
include abdominal pain, discomfort and/or bloating and constipation symptoms (e.g., incomplete evacuation, infrequent bowel
movements, hard/lumpy stools), while CIC is primarily characterized by constipation symptoms.
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Greater than 65% of IBS-C patients suffer from bloating and/or discomfort at least one time per week, according to the
Lieberman Survey.
Linaclotide—U.S. 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). We and AbbVie began commercializing LINZESS in
the U.S. in December 2012. In January 2017, the U.S. FDA approved a 72 mcg dose of linaclotide for the treatment of adult
men and women with CIC.
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. In September 2020,
based on the Phase IIIb data of linaclotide 290 mcg on the overall abdominal symptoms of bloating, pain and discomfort, in
adult patients with IBS-C, the U.S. FDA approved our supplemental new drug application to include a more comprehensive
description of the effects of LINZESS in its approved label.
In addition, we and AbbVie have established a nonclinical and clinical post-marketing plan with the U.S. FDA to
understand the safety and efficacy of LINZESS in pediatric patients. In August 2021, the U.S. FDA approved a revised label
for LINZESS based on clinical safety data that had been generated thus far in pediatric studies. The updated label modified the
boxed warning for risk of serious dehydration and contraindication against use in children to those less than two years of age.
The boxed warning and contraindication previously applied to all children less than 18 years of age and less than 6 years of
age, respectively. 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.
Linaclotide—Global. AbbVie has rights to develop and commercialize linaclotide in all countries worldwide other
than China (including Hong Kong and Macau) and Japan. CONSTELLA is the first, and to date, only drug approved in the
European Union, or E.U., for IBS-C. CONSTELLA first became commercially available in certain European countries
beginning in 2013. AbbVie is commercializing CONSTELLA in a number of European countries, including the United
Kingdom, Italy and Spain for adults with IBS-C.
AbbVie has exclusive rights to commercialize linaclotide in Canada as CONSTELLA and in Mexico as LINZESS.
CONSTELLA became commercially available in Canada in 2014 for adults with IBS-C or CIC and in 2024 for pediatric
patients ages 6-17 years-old with FC. LINZESS became commercially available in Mexico in 2014 for adults with IBS-C or
CIC.
Astellas has rights to develop, manufacture and commercialize linaclotide in Japan. Astellas began commercializing
LINZESS in Japan for adults with IBS-C in 2017, and for adults with chronic constipation in 2018.
AstraZeneca has rights to develop, manufacture and commercialize linaclotide in China (including Hong Kong and
Macau). In 2019, AstraZeneca began commercializing LINZESS in China for adults with IBS-C.
Apraglutide
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.
SBS is a malabsorption disorder caused by the loss of functional small intestine, with symptoms that include
diarrhea, dehydration, malnutrition and weight loss. SBS typically occurs in adults as a consequence of irreparable GI damage
caused by physical trauma, Crohn’s disease, ulcerative colitis, ischemia or cancer requiring surgeries that result in the removal
of large portions of the small intestine or colon. In infants and children, SBS is typically a consequence of congenital defects
or decreases in intestinal absorptive capacity secondary to surgical procedures. The symptoms and severity of SBS can vary
depending upon the length and function of the remaining portion of the intestine. Patients suffer from SBS-IF when their gut
function is reduced below the minimum function necessary for the absorption of macronutrients or water and electrolytes
required to survive and, in the case of infants and children, to maintain health and growth.
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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. 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 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.
IW-3300
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 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.
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. 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. We also intend to establish
strong global brands by out-licensing development and commercialization rights to our products in other key territories to
high-performing partners. 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. and enabled partners with strong global capabilities to commercialize linaclotide in
territories outside of the U.S.
The following chart shows our revenue for the U.S. and the rest of the world as a percentage of our total revenue for
each of the years ended December 31, 2024, 2023, and 2022.
Year Ended December 31,
2024
2023
2022
U.S.
97.1 % 97.8 % 98.1 %
Rest of world
2.9 %
2.2 %
1.9 %
100.0 % 100.0 % 100.0 %
Revenue attributable to our linaclotide partnerships comprised substantially all of our revenue for each of the years
indicated. Further, we currently derive a significant portion of our revenue from our LINZESS collaboration with AbbVie for
the U.S. and believe that the revenues from this collaboration will continue to constitute a significant portion of our total
revenue for the foreseeable future. Our revenue from our LINZESS collaboration with AbbVie for the U.S. 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
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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
In September 2007, we entered into a collaboration agreement with AbbVie to develop and commercialize linaclotide
for the treatment of IBS-C, CIC and other GI conditions in North America. 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. AbbVie is
solely responsible for the further development, regulatory approval and commercialization of linaclotide in those countries
and funding any costs.
License Agreement with AbbVie (All countries other than the countries and territories of North America, China (including
Hong Kong and Macau), and Japan)
In April 2009, we entered into a license agreement with Almirall, S.A., or Almirall, or the European License
Agreement, to develop and commercialize linaclotide in Europe (including the Commonwealth of Independent States and
Turkey) for the treatment of IBS-C, CIC, and other GI conditions. In October 2015, Almirall transferred its exclusive license
to develop and commercialize linaclotide in Europe to AbbVie. In January 2017, we and AbbVie entered into an amendment to
the European License Agreement. The European License Agreement, as amended, extended the license to develop and
commercialize linaclotide in all countries other than China (including Hong Kong and Macau), Japan, and the countries and
territories of North America. We refer to the additional licensed countries as the Expanded Territory. Under the European
License agreement, AbbVie is obligated to pay us (i) certain commercial milestones totaling up to $42.5 million, (ii) royalties
based on sales volume in Europe, beginning in the mid-single digits percent and escalating to the upper-teens percent, and (iii)
on a country-by-country and product-by-product basis in the Expanded Territory, a royalty as a percentage of net sales of
products containing linaclotide as an active ingredient in the upper-single digits for five years following the first commercial
sale of a linaclotide product in a country, and in the low-double digits thereafter. The royalty rate for products in the Expanded
Territory will decrease, on a country-by-country basis, to the lower-single digits, or cease entirely, following the occurrence of
certain events.
License Agreement for Japan with Astellas
In November 2009, we entered into a license agreement with Astellas to develop and commercialize linaclotide for
the treatment of IBS-C, CIC, and other GI conditions in Japan. On August 1, 2019, we and Astellas amended and restated the
license agreement. Under the terms of the amended and restated license agreement, Astellas is obligated to pay royalties to us
at rates beginning in the mid-single-digits percent and escalating to low-double-digits percent, based on aggregate annual net
sales in Japan of products containing linaclotide active pharmaceutical ingredient, or API.
Collaboration Agreement for China (including Hong Kong and Macau), with AstraZeneca
In October 2012, we entered into a collaboration agreement with AstraZeneca to co-develop and co-commercialize
linaclotide in China (including Hong Kong and Macau). In September 2019, we and AstraZeneca amended and restated the
collaboration agreement, under which AstraZeneca obtained the exclusive right to develop, manufacture and commercialize
products containing linaclotide in the territory. Under the terms of the amended and restated agreement, we transferred all
manufacturing responsibilities in China (including Hong Kong and Macau) to AstraZeneca, and we were entitled to receive
non-contingent payments totaling $35.0 million in three installments through 2024, with the final installment collected during
the first quarter of 2024. In addition, AstraZeneca may be required to make milestone payments totaling up to $90.0 million
contingent on the achievement of certain sales targets and is required to pay tiered royalties to us at rates beginning in the mid-
single-digits percent and increasing up to twenty percent based on the aggregate annual net sales of products containing
linaclotide in the territory.
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Development and Commercialization Agreement with AKP
In March 2022, VectivBio entered into a development and commercialization agreement with Asahi Kasei Pharma
Corporation, or AKP, in which VectivBio granted an exclusive license to AKP, with the right to sublicense in multiple tiers, to
develop, commercialize and exploit products derived from apraglutide in Japan.
Pursuant to the terms of the development and commercialization agreement with AKP, VectivBio received an upfront
payment of JPY 3,000 million ($24.6 million at date of agreement) and development-related payments of JPY 1,600 million in
the aggregate ($13.1 million at date of agreement) and is eligible to receive development milestones of JPY 1,000 million
($8.2 million at date of agreement) and up to JPY 19,000 million ($155.8 million at date of agreement) of commercial and
sales-based milestone payments. VectivBio is also eligible to receive payments in the commercial period for manufacturing
supply equal to cost-plus manufacturing mark-up and tiered royalties of up to a mid-double-digit percentage on product sales
continuing until the later of (i) expiration of regulatory exclusivity in Japan, or (ii) expiration of the last valid patent claim that
provides exclusivity to apraglutide in Japan, or the Royalty Term. The development and commercialization agreement will
terminate upon the expiration of the Royalty Term.
Our Strategy
Our strategy is focused on three core priorities: maximize LINZESS, advance our GI pipeline, and deliver sustained
profits and cash flow.
Key elements of our strategy include:
Maximize LINZESS
●
Leveraging our U.S.-focused commercial capabilities with our partner, AbbVie, to expand the commercial
potential of LINZESS.
●
Exploring development opportunities to enhance the clinical profile of LINZESS by studying linaclotide in
additional indications, populations, and formulations.
●
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
●
Executing our strategy by delivering sustainable profits and cash flows.
●
Applying a thoughtful and disciplined capital allocation strategy to deliver value for our shareholders over
the long-term.
Competition
Linaclotide competes globally with certain branded and generic prescription therapies and over-the-counter, or OTC,
products for the treatment of IBS-C and CIC, or their associated symptoms.
OTC laxatives make up the majority of the treatments in the U.S. for IBS-C and CIC, according to our research.
LINZESS is the number one prescribed branded treatment in the U.S. for adults with IBS-C and CIC, according to 2024 data
from IQVIA Inc. National Prescription Audit.
Until the launch of LINZESS, the only available branded prescription therapy for IBS-C and CIC in the U.S. was
AMITIZA® (lubiprostone), which is approved for the treatments of CIC, IBS-C and opioid induced constipation. Takeda
Pharmaceuticals Limited, or Takeda’s AMITIZA is approved for commercialization in the U.S. and in certain European
countries, including the United Kingdom and Switzerland by Sucampo AG, for the treatment of adults with CIC, and for the
treatment of chronic constipation in Japan by Mylan N.V. Authorized generic versions of AMITIZA have been available in the
U.S. since January 2021. TRULANCE® (plecanatide) was approved in the U.S. for the
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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. Ardelyx, Inc.’s,
or Ardelyx, IBSRELA™ (tenapanor), is approved by the U.S. FDA for the treatment for IBS-C in adults, and Vibrant Gastro
Inc’s. Vibrant, a drug-free capsule, is approved by the U.S. FDA for the treatment of CIC in adults who have not experienced
relief of their bowel symptoms by using laxative therapies at the recommended dosage for at least one month. OTC laxatives
such as MiraLAX® and DULCOLAX®, and lactulose, a prescription laxative treatment, are also available for the treatment of
constipation.
In addition, any product candidates that we successfully develop and commercialize will compete with existing drugs
and new drugs that may become available in the future. 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. 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. Products with other mechanisms of action may emerge as future competition.
Manufacturing and Supply
Linaclotide
It is our objective that the supply of linaclotide be safe and effective, with redundancy built into critical steps of the
supply chain, and that each of our collaboration partners are in a position to manage the supply and distribution of linaclotide
in their respective territories through a combination of contract manufacturers and in-house manufacturing capabilities.
Linaclotide production consists of three phases—manufacture of the active pharmaceutical ingredient, or API (sometimes
referred to as drug substance), manufacture of finished drug product and manufacture of finished goods. We and/or our
partners have commercial supply agreements with multiple third-party manufacturers for the production of linaclotide API.
We believe the current commercial suppliers have the capabilities to produce linaclotide API in accordance with current good
manufacturing practices, or GMP, on a sufficient scale to meet the worldwide development and commercial needs for
linaclotide. The commercial suppliers of linaclotide API are subject to routine inspections by regulatory agencies worldwide
and also undergo periodic audit and certification by our partners’ or our own quality department.
Each of AbbVie, Astellas and AstraZeneca is responsible for linaclotide API, finished drug product and finished
goods manufacturing (including bottling and packaging) and distributing the finished goods to wholesalers in its respective
territories.
Prior to linaclotide, there was no precedent for long-term room temperature shelf storage formulation for an orally
dosed peptide to be produced in millions of capsules per year. Our efforts to date have led to formulations that are both cost
effective and able to meet the stability requirements for commercial pharmaceutical products.
Apraglutide
We do not currently own or operate manufacturing facilities for the production of clinical, or, if approved,
commercial quantities of apraglutide. We design and develop the manufacturing process for apraglutide together with contract
development and manufacturing organizations, or CDMOs. We utilize these CDMOs to manufacture apraglutide for human
use. Although we intend to rely on third-party CDMOs to produce apraglutide, we have personnel with experience managing
third-party CDMOs producing apraglutide in clinical or commercial quantities.
Our clinical trials of apraglutide currently use the product in the form of a lyophilized powder in vial that is
solubilized and reconstituted with a diluent prior to injection. We are also evaluating novel drug product presentations for
further development, with the goal of providing increased patient convenience and increased simplicity of the dosing and self-
injection.
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Sales and Marketing
For the foreseeable future, in the U.S., we intend to develop and commercialize LINZESS with our partner, AbbVie,
and apraglutide, if approved, alone. In territories outside the U.S., we expect to rely on partners to develop and commercialize
our products and product candidates. 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 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. and with partners in territories outside the U.S. For example, we granted AKP an exclusive
license to sublicense, develop, commercialize and exploit products derived from apraglutide in Japan. We are considering
potential partnerships in other territories outside the U.S.
Patents and Proprietary Rights
We actively seek to protect the proprietary technology that we consider important to our business, including pursuing
patents that cover our products, compositions, and formulations, their methods of use and the processes for their manufacture,
as well as any other relevant inventions and improvements that are commercially important to the development of our
business. We also rely on trade secrets that may be important to the development of our business.
Our success will depend significantly on our ability to obtain and maintain patent and other proprietary protection for
the technology, inventions and improvements we consider important to our business; defend our patents; preserve the
confidentiality of our trade secrets; and operate without infringing the patents and proprietary rights of third parties.
The term of individual patents depends upon the legal term of the patents in the countries in which they are obtained.
In most countries in which we file, the patent term is 20 years from the date of filing the non-provisional application. We
expect to apply, and have applied, for patent term extension in countries where it is available.
Linaclotide Patent Portfolio
After the recent expiration of a number of patents in our linaclotide patent portfolio, our linaclotide patent portfolio is
currently composed of 11 patents in the U.S., including 7 U.S. 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.
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. In
addition, the commercial formulations of the 72 mcg, 145 mcg and 290 mcg LINZESS doses are covered by patents in the
U.S. that expire in the early 2030s. The granted, unexpired European patents, which will expire between 2027 and 2036, 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. The granted,
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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.
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.
The patent term of a patent that covers a U.S. FDA approved drug is also eligible for patent term extension, which
permits patent term extension as compensation for some of the patent term lost during the U.S. FDA regulatory review
process. The Hatch Waxman Act permits a patent term extension of a single patent applicable to an approved drug for up to
five years beyond the expiration of the patent, but the extension cannot extend the remaining term of a patent beyond a total of
14 years from the date of product approval by the U.S. FDA. The United States Patent and Trademark Office has issued a
Certificate of Patent Term Extension for U.S. Patent 7,304,036, which covers linaclotide and methods of use thereof. As a
result, the patent term of this patent was extended to August 30, 2026, 14 years from the date of linaclotide’s approval by the
U.S. FDA. Similar provisions are available in Europe and certain other foreign jurisdictions to extend the term of a patent that
covers an approved drug. We have received patent term extensions in Japan for several of our linaclotide patents. We have also
received patent term extensions, called supplementary protection certificates, for certain linaclotide patents from several
national patent offices in Europe.
We and AbbVie received Paragraph IV certification notice letters regarding abbreviated new drug applications, or
ANDAs, submitted to the U.S. FDA by five generic drug manufacturers requesting approval to engage in commercial
manufacture, use, sale and offer for sale of linaclotide capsules (72 mcg, 145 mcg and 290 mcg), proposed generic versions of
LINZESS. All five manufacturers requested approval for their 145 mcg and 290 mcg generic doses of LINZESS and two
requested additional approval for their 72 mcg generic doses of LINZESS. We and AbbVie have entered into settlement
agreements with all five of these generic drug manufacturers providing for licenses to market their 72 mcg (if applicable), 145
mcg and 290 mcg generic versions of LINZESS, beginning as early as March 2029 (subject to U.S. FDA Approval), unless
certain limited circumstances, customary for settlement agreements of this nature, occur.
Apraglutide Patent Portfolio
Our apraglutide patent portfolio includes a patent family which we exclusively license that is composed of one issued
U.S. patent and 56 foreign patents. 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. are
issued in Europe, Japan, China, Australia, Canada, as well as other jurisdictions. The issued European patent is validated and
issued in 37 countries, including Germany, the United Kingdom, France, Italy and Spain. 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. 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. and foreign patent applications contain composition-of-matter claims to ultrapure compositions of
apraglutide, methods of manufacturing apraglutide, and methods of treatment using apraglutide. 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 U.S. 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. and foreign patents granted from the pending patent applications would be expected to expire in
2042.
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Government Regulation
Our business is subject to government regulation in the U.S., E.U., and in other countries. The U.S. FDA, the
European Medicines Agency, or EMA, and other regulatory authorities have very broad enforcement authority and failure to
abide by applicable regulatory requirements can result in administrative or judicial sanctions being imposed on us, including
warning letters, refusals of government contracts, clinical holds, civil penalties, injunctions, restitution, disgorgement of
profits, recall or seizure of products, total or partial suspension of production or distribution, withdrawal of approval, refusal
to approve pending applications, and civil or criminal prosecution. Within the U.S., in addition to the U.S. FDA, numerous
federal, state and local authorities have jurisdiction over, or enforce laws related to, such activities, including the U.S. Drug
Enforcement Agency, Centers of Medicare & Medicaid Services, or CMS, the Department of Health and Human Services, or
HHS, the U.S. Department of Justice, state Attorneys General, state departments of health and state pharmacy boards.
U.S. FDA Approval Process
In the U.S., pharmaceutical products are subject to extensive regulation by the U.S. FDA. The Federal Food, Drug
and Cosmetic Act, or FDCA, and other federal and state statutes and regulations, as well as similar foreign regulations,
govern, among other things, the research, development, testing, manufacture, storage, recordkeeping, approval, labeling,
promotion and marketing, distribution, post-marketing requirements and assessments, post-approval monitoring and reporting,
sampling, pricing reimbursement and import and export of pharmaceutical products.
No company may market a new drug in the U.S. until it has submitted an NDA to the U.S. FDA, and the U.S. FDA
has approved it. The steps required before the U.S. FDA may approve an NDA generally include:
●
conducting non-clinical laboratory tests and animal tests in compliance with U.S. FDA’s good laboratory
practice, or GLP, requirements;
●
design of a clinical protocol and submission to the U.S. FDA of an investigational new drug application, or IND,
for human clinical testing, which must become effective before human clinical trial may begin;
●
approval by an institutional review board, or IRB, representing each clinical site before each clinical trial may be
initiated;
●
development, manufacture and testing of active pharmaceutical product and dosage forms suitable for human
use in compliance with current GMP;
●
conducting adequate and well-controlled human clinical trials that establish the safety and efficacy of the
product for its specific intended use(s), in accordance with good clinical practices, or GCP;
●
preparation and submission to the U.S. FDA of an NDA;
●
review of the NDA by a U.S. FDA advisory committee, where applicable;
●
satisfactory completion of one or more U.S. FDA inspections of the manufacturing facility or facilities at which
the product, or components thereof, are produced to assess compliance with current GMP requirements and to
assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality
and purity;
●
satisfactory completion of any U.S. FDA inspections of non-clinical and clinical trial sites to assure compliance
with GLP and GCP requirements; and
●
U.S. 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. FDA.
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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. 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. FDA as part of an IND, which must become
effective before we may commence human clinical trials in the U.S. The IND will automatically become effective 30 days
after its receipt by the U.S. FDA, unless the U.S. FDA raises concerns or questions before that time about the conduct of the
proposed trial. In such a case, we must work with the U.S. FDA to resolve any outstanding concerns before the clinical trial
can proceed. We cannot be sure that submission of an IND will result in the U.S. FDA allowing clinical trials to begin, or that,
once begun, issues will not arise that will cause us or the U.S. FDA to modify, suspend or terminate such trials. The study
protocol and informed consent information for patients in clinical trials must also be submitted to an IRB, for approval. An
IRB may also require the clinical trial at the site to be halted, either temporarily or permanently, for failure to comply with the
IRB requirements or if the trial has been associated with unexpected serious harm to subjects. An IRB may also impose other
conditions on the trial. For studies conducted outside of the U.S., similarly, we are subject to local regulations which may
differ from the U.S. and local regulations must be followed appropriately. Additionally, some clinical trials are overseen by an
independent group of qualified experts organized by the clinical trial sponsor, known as a data monitoring committee. This
group may recommend continuation of the trial as planned, changes in trial conduct, or cessation of the trial at designated
checkpoints based on access to certain data from the trial.
Clinical trials involve the administration of the product candidate to humans under the supervision of qualified
investigators, generally physicians not employed by or under the trial sponsor’s control. 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. 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; and
●
identify possible adverse effects and safety risks.
Phase III trials generally 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.
The U.S. 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. FDA requirements or presents an
unacceptable risk to the clinical trial patients. We may also suspend clinical trials at any time on various grounds.
Sponsors of clinical trials of certain U.S. FDA-regulated products, including prescription drugs, are required to
register and disclose certain clinical trial information on a public registry maintained by the National Institutes of Health. 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.
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. FDA in the form of an NDA requesting
approval to market the drug. The U.S. FDA approval of the NDA is required before marketing of the product may begin in the
U.S. If the NDA contains all pertinent information and data, the U.S. FDA will “file” the application and begin review. In the
event it does not, the U.S. FDA will issue a “refuse-to-file” determination and request additional information before filing the
NDA. U.S. FDA reviews an NDA pursuant to certain timelines and goals established by the Prescription Drug User Fee Act.
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. The U.S. FDA may
refer an application to an advisory committee for review, evaluation and
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recommendation as to whether the application should be approved. The U.S. FDA is not bound by the recommendations of an
advisory committee, but it considers such recommendations carefully when making decisions. Before approving an NDA, the
U.S. FDA will typically inspect the facilities at which the product candidate is manufactured and will not approve the product
candidate unless current GMP compliance is satisfactory. The U.S. FDA also typically inspects facilities responsible for
performing animal testing, as well as clinical investigators who participate in clinical trials. The U.S. FDA may refuse to
approve an NDA if applicable regulatory criteria are not satisfied or may require additional testing or information. If the U.S.
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. Once granted, product approvals may be
withdrawn if compliance with regulatory standards is not maintained or problems are identified following initial marketing.
The testing and approval process requires substantial time, effort and financial resources, and our product candidates
may not be approved on a timely basis, if at all. The time and expense required to perform the clinical testing necessary to
obtain U.S. FDA approval for regulated products can frequently exceed the time and expense of the research and development
initially required to create the product. The results of non-clinical studies and initial clinical trials of our product candidates
are not necessarily predictive of the results from large-scale clinical trials, and clinical trials may be subject to additional costs,
delays or modifications due to a number of factors, including difficulty in obtaining enough patients, investigators or product
candidate supply. Failure by us or our collaborators, licensors or licensees to obtain, or any delay in obtaining, regulatory
approvals or in complying with requirements could adversely affect commercialization and our ability to receive product or
royalty revenues.
Hatch-Waxman Act
The Hatch-Waxman Act established abbreviated approval procedures for generic drugs. Approval to market and
distribute these drugs is obtained by submitting an ANDA with the U.S. FDA. The application for a generic drug is
“abbreviated” because it need not include non-clinical or clinical data to demonstrate safety and effectiveness and may instead
rely on the U.S. FDA’s previous finding that the brand drug, or reference drug, is safe and effective. In order to obtain
approval of an ANDA, an applicant must, among other things, establish that its product is bioequivalent to an existing
approved drug and that it has the same active ingredient(s), strength, dosage form, and route of administration. A generic drug
is considered bioequivalent to its reference drug if testing demonstrates that the rate and extent of absorption of the generic
drug is not significantly different from the rate and extent of absorption of the reference drug when administered under similar
experimental conditions.
The Hatch-Waxman Act also provides incentives by awarding, in certain circumstances, certain legal protections
from generic competition. This protection comes in the form of a non-patent exclusivity period, during which the U.S. FDA
may not accept, or approve, an application for a generic drug, whether the application for such drug is submitted through an
ANDA or a through another form of application, known as a 505(b)(2) application. This type of NDA authorizes the U.S. FDA
to approve a follow-on product on the basis of, among other things, the U.S. FDA’s previous findings of safety and
effectiveness for a reference product.
The Hatch-Waxman Act grants five years of regulatory exclusivity when a company develops and gains NDA
approval of a new chemical entity that has not been previously approved by the U.S. FDA. This exclusivity provides that the
U.S. FDA may not accept an ANDA or 505(b)(2) application for five years after the date of approval of previously approved
drug, or four years in the case of an ANDA or 505(b)(2) application that challenges a patent claiming the reference drug (see
discussion below regarding Paragraph IV Certifications). The Hatch-Waxman Act also provides three years of regulatory
exclusivity for approved applications for drugs that are not new chemical entities, if the application contains the results of new
clinical investigations (other than bioavailability studies) conducted or sponsored by the applicant that were essential to
approval of the application. Examples of applications that may require new clinical investigations essential to approval and
receive three-year exclusivity include applications for new indications, dosage forms (including new drug delivery systems),
strengths, or conditions of use for an already approved product. This three-year exclusivity period only protects against U.S.
FDA approval of ANDAs and 505(b)(2) applications for generic drugs for the conditions of approval (for example, indication
or dosage form) that required new clinical investigations that were essential to approval; it does not prohibit the U.S. FDA
from accepting or approving ANDAs or 505(b)(2) NDAs for generic drugs that do not include such conditions of approval.
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Paragraph IV Certifications. Under the Hatch‑Waxman Act, NDA applicants and NDA holders must provide
information about certain patents claiming their drugs, or methods of use of the drug that is the subject of the NDA, for listing
in the Orange Book. 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 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. FDA can approve the ANDA or 505(b)(2) application
containing the Paragraph III certification upon expiration of the patent.
Within 20 days of the acceptance by the U.S. FDA of an ANDA or 505(b)(2) application containing a Paragraph IV
certification, the applicant must notify the NDA holder and patent owner that the application has been submitted and provide
the factual and legal basis for the applicant’s opinion that the patent is invalid, unenforceable, or not infringed. The NDA
holder or patent holder may then initiate a patent infringement suit in response to the Paragraph IV notice. If this is done
within 45 days of receiving notice of the Paragraph IV certification, a 30‑month stay of the U.S. FDA’s ability to approve the
ANDA or 505(b)(2) application is triggered. The U.S. FDA may approve the proposed product before the expiration of the
30‑month stay only if a court finds the patent invalid or not infringed, and the court may shorten or lengthen the 30-month stay
under certain limited circumstances.
Patent Term Extension. Under the Hatch‑Waxman Act, a portion of the patent term lost during product development
and U.S. FDA review of an NDA or 505(b)(2) application is extended if approval of the application is the first permitted
commercial marketing of a drug containing the active ingredient. The patent term extension period is generally one‑half the
time between the effective date of the IND and the date of submission of the NDA, plus the time between the date of
submission of the NDA and the date of U.S. FDA approval of the product. The maximum period of patent term extension is
five years, and the patent cannot be extended to more than 14 years from the date of U.S. FDA approval of the product. Only
one unexpired patent claiming the drug product, a method of using the product or a method of manufacturing the product is
eligible for extension and the patent holder must apply for extension within 60 days of approval. The U.S. Patent and
Trademark Office, or USPTO, in consultation with the U.S. FDA, reviews and approves the application for patent term
extension.
Orphan Drug Designation and Exclusivity
Orphan drug designation in the U.S. is designed to encourage sponsors to develop products intended for the treatment
of rare diseases or conditions. In the U.S., a rare disease or condition is statutorily defined as a condition that affects fewer
than 200,000 individuals in the U.S. or that affects more than 200,000 individuals in the U.S. and for which there is no
reasonable expectation that the cost of developing and making the product available for the disease or condition will be
recovered from sales of the product in the U.S.
Orphan drug designation qualifies a company for certain tax credits. In addition, if a product candidate that has
orphan drug designation subsequently receives the first U.S. FDA approval for that drug for the disease for which it has such
designation, the product is entitled to orphan drug exclusivity, which means that the U.S. FDA may not approve any other
applications to market the same drug for the same indication for seven years following product approval unless the subsequent
product candidate is demonstrated to be clinically superior on the basis of greater efficacy or safety, or by providing a major
contribution to patient care. Absent a showing of clinical superiority, the U.S. 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.
Regulation of Drug-Device Combination Products in the U.S.
Certain products may be comprised of components, such as drug components and device components that would
normally be subject to different regulatory frameworks by the U.S. FDA and frequently regulated by different centers at the
U.S. FDA. These products are known as drug-device combination products. 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. The determination of which center will be the lead center is based on the “primary mode of
action” of the drug-device combination product. Thus, if the primary mode of action of a drug-device combination product is
attributable to the drug product, the U.S. FDA center responsible for premarket review of the drug product would have
primary jurisdiction for the drug-device combination product. The U.S. FDA has also
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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. It is also responsible for developing guidance and regulations to clarify the regulation of combination products, and
for assignment of the U.S. FDA center that has primary jurisdiction for review of drug-device combination products where the
jurisdiction is unclear or in dispute.
A drug-device combination product with a primary mode of action attributable to the drug component generally
would be reviewed and approved pursuant to the drug approval processes set forth in the FDCA. In reviewing the NDA for
such a product, however, U.S. FDA reviewers could consult with their counterparts in the device center to ensure that the
device component of the combination product met applicable requirements regarding safety, effectiveness, durability and
performance. Approval may require the performance of certain clinical studies, such as clinical usability or human factors
studies to demonstrate the safety and/or effectiveness of the device component of the combination product. In addition, under
U.S. FDA regulations, drug-device combination products are subject to current GMP requirements applicable to both drugs
and devices, including the Quality System Regulations applicable to medical devices.
Other U.S. Regulatory Requirements
After approval, finished drug products are subject to extensive continuing regulation by the U.S. FDA, which
includes company obligations to manufacture products in accordance with current GMP, maintain and provide to the U.S.
FDA updated safety and efficacy information, report adverse experiences with the product, keep certain records and submit
periodic reports, obtain U.S. FDA approval of certain manufacturing or labeling changes, and comply with U.S. FDA
promotion and advertising requirements and restrictions. Failure to meet these obligations can result in various adverse
consequences, both voluntary and U.S. FDA-imposed, including product recalls, withdrawal of approval, restrictions on
marketing, and the imposition of civil fines and criminal penalties against the NDA holder. In addition, later discovery of
previously unknown safety or efficacy issues may result in restrictions on the product, manufacturer or NDA holder.
We and our partners and any third-party manufacturers we or our partners engage are required to comply with
applicable U.S. FDA manufacturing requirements contained in the U.S. FDA’s current GMP regulations. Current GMP
regulations require, among other things, quality control and quality assurance as well as the corresponding maintenance of
records and documentation. The manufacturing facilities for our products must meet current GMP requirements to the
satisfaction of the U.S. FDA pursuant to a pre-approval inspection before we can use them to manufacture our products. We
and any third-party manufacturers are also subject to periodic inspections of facilities by the U.S. FDA and other authorities,
including procedures and operations used in the testing and manufacture of our products to assess our compliance with
applicable regulations.
With respect to post-market product advertising and promotion, the U.S. FDA imposes a number of complex
regulations on entities that advertise and promote pharmaceuticals, which include, among others, standards for direct-to-
consumer advertising, prohibitions on promoting drugs for uses, conditions or diseases, or in patient populations that are not
consistent with the drug’s approved labeling (known as “off-label use”), and principles governing industry-sponsored
scientific and educational activities. Failure to comply with U.S. FDA requirements can have negative consequences,
including adverse publicity, warning or untitled letters from the U.S. FDA, mandated corrective advertising or
communications with doctors or patients, and civil or criminal penalties. Although physicians may prescribe legally available
drugs for off-label uses, manufacturers may not market or promote such off-label uses. In January 2025, the U.S. FDA
published final guidance outlining the agency’s non-binding policies governing the distribution of scientific information on
unapproved uses to healthcare providers. 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.
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. FDA approval of a new NDA or sNDA before the
change can be implemented. An sNDA for a new indication typically requires clinical data similar in type and quality to the
clinical data supporting the original application for the original indication, and the U.S. FDA uses similar procedures and
actions in reviewing such sNDAs as it does in reviewing NDAs.
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Adverse event reporting and submission of periodic reports are required following U.S. FDA approval of an NDA.
The U.S. FDA also may require post marketing testing, known as Phase IV testing, REMS, and surveillance to monitor the
effects of an approved product or to place conditions on an approval that restrict the distribution or use of the product.
Outside the U.S., our and our collaborators’ abilities to market a product are contingent upon receiving marketing
authorization from the appropriate regulatory authorities. The requirements governing the conduct of clinical trials, marketing
authorization, pricing and reimbursement vary widely from jurisdiction to jurisdiction. At present, foreign marketing
authorizations are applied for at a national level, although within the E.U. registration procedures are available to companies
wishing to market a product in more than one E.U. member state. We are subject to U.S. federal and foreign anti-corruption
laws. Those laws include the U.S. Foreign Corrupt Practices Act, or FCPA, which prohibits U.S. corporations and their
representatives from offering, promising, authorizing, or making payments to any foreign government official, government
staff member, political party or political candidate in an attempt to obtain or retain business abroad. The scope of the FCPA
encompasses certain healthcare professionals in many countries. We are also subject to similar laws of other countries that
have enacted anti-corruption laws and regulations.
EU Marketing Approval of Medicinal Products
In order to market any product outside of the U.S., a company also must comply with numerous and varying
regulatory requirements of other countries and jurisdictions regarding quality, safety and efficacy and governing, among other
things, clinical trials, marketing authorization, commercial sales and distribution of products. Regardless of whether or not it
obtains U.S. FDA approval for a product, an applicant will need to obtain the necessary marketing approvals by the
comparable foreign regulatory authorities before it can initiate clinical trials or marketing of the product in those countries or
jurisdictions. Specifically, there are a number of similarities between the process regarding regulatory approval of medicinal
products in the European Economic Area, or EEA, and that in the U.S. Marketing approval requires satisfactory completion of
pharmaceutical development, non-clinical studies and adequate and well-controlled clinical trials to establish the safety and
efficacy of the medicinal product for each proposed indication. It also requires the submission to relevant competent
authorities for a clinical trial authorization to be granted and to the EMA, or to competent authorities in E.U. Member States
for granting of a marketing authorization by these authorities before the product can be marketed and sold in the E.U.
Clinical Trial Approval. Similar to the U.S., the various phases of preclinical and clinical research in the E.U. are
subject to significant regulatory controls. Certain preclinical (also termed “non-clinical”) data is required in order to inform
the scientific basis for clinical trials to be conducted and later for such data to be used in the dossier for supporting a
marketing authorization application, or MAA. Preclinical data are required to guide the clinical development, from Phase I
(first-in-human clinical trials) through to Phases II and III, to establish the safety and efficacy of a medicinal product. During
all phases of clinical development, national competent authorities of E.U. Member States and other comparable regulatory
authorities require extensive monitoring and auditing of all clinical trial related activities, to ensure safety of the trial
participants, and quality and integrity of trial data.
In the E.U., clinical trials are governed by the Clinical Trials Regulation (E.U.) No. 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. Prior to commencing a clinical trial, the sponsor must obtain a clinical trial authorization from
competent authorities of E.U. Member States in which the sponsor intends on carrying out clinical trials, and a positive
opinion from an independent Ethics Committee. The CTR, which is directly applicable in all E.U. Member States, introduces
a streamlined application procedure through a single-entry point, the “E.U. portal”, the Clinical Trials Information System, or
CTIS. Since January 31, 2023, the use of CTIS has become mandatory for all clinical trial sponsors submitting initial
applications for the approval of their clinical trials in the E.U. The CTR also establishes a single set of documents to be
prepared and submitted for the application including, among other things, a copy of the trial protocol and an investigational
medicinal product dossier containing information about the manufacture and quality of the medicinal product under
investigation as well as simplified reporting procedures for clinical trial sponsors.
Ongoing clinical trials authorized under CTD with at least one active site in the E.U. on January 30, 2025 needed to
be transitioned to CTR. Active site in the context of transitioning means that the last visit of the last subject, or the other trial-
related interventions with the subject specified in the protocol, will take place after January 30, 2025.
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Clinical trials with no active sites authorized under CTD do not need to be transitioned even if the global trial is still ongoing
outside the E.U. after the transition deadline.
Clinical trials of medicinal products in the E.U. must be conducted in accordance with current good clinical practices
requirements and the applicable regulatory requirements, including those foreseen in the Good Clinical Practice Directive
2005/28/EC, and the ethical principles that have their origin in the Declaration of Helsinki. Studies should also be conducted
in accordance with all applicable EMA, European Commission and national guidelines. Medicinal products used in clinical
trials must be manufactured in accordance with the guidelines on current GMP, and in a GMP compliant facility, which can be
subject to GMP inspections.
Marketing Authorization. To obtain a marketing authorization to market a medicinal product in the EEA, an applicant
must submit an MAA, either in accordance with a centralized procedure administered by the EMA or one of the procedures
administered by competent authorities in E.U. Member States (decentralized procedure, national procedure or mutual
recognition procedure). A marketing authorization may be granted only to an applicant established in the E.U.
The centralized procedure provides for the grant of a single marketing authorization by the European Commission
that is valid in all E.U. Member States and through the EEA Member States – Norway, Iceland and Liechtenstein. Pursuant to
Regulation (EC) No 726/2004, the centralized procedure is compulsory for specific medicinal products, including those (i)
derived from biotechnological processes, (ii) designated as orphan medicinal products, (iii) that are classified as advanced
therapy medicinal products, or ATMPs, and (iv) containing a new active substance indicated for the treatment of HIV/AIDS,
cancer, neurodegenerative diseases, diabetes, auto-immune and other immune dysfunctions and viral diseases. For medicinal
products containing a new active substance indicated for the treatment of other diseases and products that are highly
innovative or for which a centralized process is in the interest of patients, authorization through the centralized procedure is
optional for product approval.
Under the centralized procedure, the EMA’s Committee for Medicinal Products for Human Use, or CHMP, conducts
the scientific assessment of a medicinal product in respect of its safety, quality and efficacy for the purpose of determining its
approvability.
Under the centralized procedure in the EEA, the maximum timeframe for the evaluation of an MAA is 210 days,
excluding clock stops. Procedural clock-stops provide the applicant with the time to gather additional information in response
to the outstanding questions raised by the CHMP. Accelerated assessment may be accepted by the CHMP in exceptional cases,
when a medicinal product is considered to be of major interest from the point of view of public health, and, in particular, from
the viewpoint of therapeutic innovation. If the CHMP accepts a request for accelerated assessment, the time limit of 210 days
will be reduced to 150 days. The CHMP can, however, revert to the standard time limit for the centralized procedure if it
considers that it is no longer appropriate to conduct an accelerated assessment.
A marketing authorization granted under the E.U. regulatory system is valid for five years. The MA may be renewed
after five years on the basis of a re-evaluation of the risk-benefit balance by the EMA or by the competent authority of the
E.U. 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. The European Commission or the competent authorities of the E.U.
Member States may decide on justified grounds relating to pharmacovigilance, to proceed with one further five-year renewal
period for the MA. Thereafter, the MA shall be valid for an unlimited period. Any authorization which is not followed by the
actual placing of the medicinal product on the E.U. market (for a centralized MA) or on the market of the authorizing E.U.
Member State within three years after authorization ceases to be valid (the so-called sunset clause).
Innovative products that target an unmet medical need and are expected to be of major public health interest may be
eligible for a number of expedited development and review programs, such as the Priority Medicines, or PRIME, scheme,
which provides incentives similar to the breakthrough therapy designation in the U.S. PRIME is a voluntary scheme aimed at
enhancing the EMA’s support for the development of medicinal products that target unmet medical needs. 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
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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.
Combination Products. As in the U.S., the regulation of combination drug-device products depends in large part on
which component has the primary mode of action.
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.
Orphan Medicinal Product Designation and Exclusivity. Regulation (EC) No. 141/2000, as implemented by
Regulation (EC) No. 847/2000, provides that a medicinal product can be designated as an orphan medicinal product by the
European Commission if its sponsor can establish that (1) the product is intended for the diagnosis, prevention or treatment of
a life-threatening or chronically debilitating condition; (2) either (a) such condition affects no more than five in ten thousand
persons in the E.U. when the application is made, or (b) the product, without the benefits derived from orphan status, would
not generate sufficient return in the E.U.; and (3) there exists no satisfactory method of diagnosis, prevention or treatment of
the condition in question that has been authorized in the E.U. or, if such method exists, the product will be of significant
benefit to those affected by that condition.
In the E.U., an application for designation as an orphan product can be made any time prior to the filing of the MAA.
Orphan medicinal product designation entitles a sponsor to incentives such as fee reductions or fee waivers, protocol
assistance, and access to the centralized MA procedure. Upon grant of an MA, provided that the orphan designation is
maintained following a satisfactory re-assessment by the Committee for Orphan Medicinal Products, or COMP, of the EMA of
the criteria for orphan designation, orphan medicinal products are entitled to a ten-year period of market exclusivity for the
approved therapeutic indication, which means that the EMA cannot accept another MAA, or grant an MA, or accept an
application to extend an MA for a similar product for the same indication for a period of ten years. The period of market
exclusivity is extended by two years for orphan medicinal products provided that the results of all studies conducted in
compliance with an agreed PIP are provided – even though the results do not lead to an approval of a pediatric indication, but
the results of the studies conducted are reflected in the summary of product characteristics and, if appropriate, in the package
leaflet of the medicinal product concerned. Orphan medicinal product designation does not confer any advantage in, or shorten
the duration of, the regulatory review and approval process.
The period of market exclusivity may, however, be reduced to six years if, at the end of the fifth year, it is established
that the product no longer meets the criteria on the basis of which it received orphan medicinal product destination, including
where it can be demonstrated on the basis of available evidence that the original orphan medicinal product is sufficiently
profitable not to justify maintenance of market exclusivity or where the prevalence of the condition has increased above the
threshold. 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; 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. A company may voluntarily remove a product from the register of orphan products.
Post-Approval Requirements. Where an MA is granted in relation to a medicinal product in the EEA, the holder of
the MA is required to comply with a range of regulatory requirements applicable to the manufacturing, marketing, promotion
and sale of medicinal products.
Similar to the U.S., both MA holders and manufacturers of medicinal products are subject to comprehensive
regulatory oversight by the EMA, the European Commission and/or the competent regulatory authorities of the individual
EEA countries. The holder of an MA must establish and maintain a pharmacovigilance system and appoint a qualified person
for pharmacovigilance who is responsible for oversight of that system. Key obligations include expedited reporting of
suspected serious adverse reactions and submission of periodic safety update reports, or PSURs.
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All new MAAs must include a risk management plan describing the risk management system that the company will
put in place and documenting measures to prevent or minimize the risks associated with the product. The regulatory
authorities may also impose specific obligations as a condition of the MA. Such risk-minimization measures or post-
authorization obligations may include additional safety monitoring, more frequent submission of PSURs, or the conduct of
additional clinical trials or post-authorization safety studies.
In the E.U., the advertising and promotion of medicinal products are subject to both E.U. and E.U. Member States’
laws governing promotion of medicinal products, interactions with physicians and other healthcare professionals, misleading
and comparative advertising and unfair commercial practices. Although general requirements for advertising and promotion of
medicinal products are established under E.U. law, the implementing rules in each member state may differ from one country
to another. In addition, the statutory control regime could be supplemented by the voluntary control of advertising of
medicinal products by self-regulatory bodies.
If we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things,
fines, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and
criminal prosecution.
International Regulation
In addition to regulations in the U.S. and the E.U., we could become subject to a variety of other foreign regulations
regarding development, approval, commercial sales and distribution of our products if we seek to market our product
candidates in other jurisdictions. Whether or not we obtain U.S. FDA or EMA approval for a product, we must obtain the
necessary approvals by the comparable regulatory authorities of foreign countries before we can commence clinical trials or
marketing of the product in those countries. The approval process varies from country to country and can involve additional
product testing and additional review periods, and the time may be longer or shorter than that required to obtain U.S. FDA or
EMA approval. The requirements governing, among other things, the conduct of clinical trials, product licensing, pricing and
reimbursement vary greatly from country to country. Regulatory approval in one country does not ensure regulatory approval
in another, but a failure or delay in obtaining regulatory approval in one country may negatively impact the regulatory process
in others. If we fail to comply with applicable foreign regulatory requirements, we may be subject to fines, suspension or
withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.
Pricing and Reimbursement
Within the U.S., significant uncertainty exists regarding the coverage and reimbursement status of products approved
by the U.S. FDA. Sales of our product, and any future products which obtain marketing approval, depend, in part, on the
extent to which our products will be covered by third-party payors, such as government health programs, commercial
insurance and managed healthcare organizations. The process for determining whether a third-party payor will provide
coverage for a drug or biologic typically is separate from the process for setting the price of such a product or for establishing
the reimbursement rate that the payor will pay for the product once coverage is approved. Third-party payors may limit
coverage to specific products on an approved list, also known as a formulary, which might not include all of the U.S. FDA-
approved drugs for a particular indication. 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. 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. Additionally, coverage and reimbursement for products can differ significantly from
payor to payor. One third-party payor’s decision to cover a particular product or service does not ensure that other payors will
also provide coverage for the medical product or service or will provide coverage at an adequate reimbursement rate.
The containment of healthcare costs has become a priority of federal and state governments, and the prices of drugs
and biologics have been a focus in this effort. Federal and state governments have shown significant interest in implementing
cost-containment programs, including restrictions on reimbursement and requirements for substitution of generic products.
Adoption of new or enhanced cost-containment measures could limit our net revenue and results. 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
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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. There have been and likely will continue to be
health care reform efforts. For example, federal legislation enacted in 2021 eliminated a statutory cap on Medicaid drug
rebate program rebates effective January 1, 2024. As another example, the Inflation Reduction Act, or IRA, of 2022, contains
various drug pricing and payment provisions. Among other provisions, the IRA imposes a yearly cap ($2,000 in 2025) on out-
of-pocket prescription drug prices in Medicare Part D. Additionally, the IRA, through a newly established Manufacturer
Discount Program, eliminated, effective January 1, 2025, the size of the discount on brand-name drugs that pharmaceutical
manufacturers are required to offer Medicare beneficiaries who are in the Medicare Part D coverage gap, or “donut hole,” by
significantly lowering the beneficiary maximum out-of-pocket cost and requiring pharmaceutical manufacturers to provide a
10% discount in the initial coverage phase of the plan and 20% discount in the catastrophic coverage phase of the plan on
brand-name drugs.
In addition, the IRA requires Medicare to negotiate Medicare prices for certain high-cost drugs and biologicals,
including both physician-administered products covered under Medicare Part B benefit and self-administered drugs covered
under the Medicare Part D benefit. 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). CMS will publish the
negotiated price, known as the “Maximum Fair Price”, or MFP, for each of the selected products. Manufacturers of selected
drugs would be required to offer the drug for Medicare recipients at the MFP. 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. 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. For additional information relating to pricing and reimbursement and legislative and other
reform initiatives that may affect coverage, pricing and reimbursement, see Item 1A, Risk Factors, elsewhere in this Annual
Report on Form 10-K.
Healthcare Compliance
We are also subject to various federal and state laws pertaining to health care “fraud and abuse,” including anti-
kickback laws and false claims laws, for activities related to sales of any of our products or product candidates that may in the
future receive marketing approval. Anti-kickback laws generally prohibit persons from soliciting, receiving or providing
remuneration, directly or indirectly, to induce either the referral of an individual, for an item or service or the purchasing or
ordering of a good or service, for which payment may be made under federal healthcare programs such as Medicare and
Medicaid or, in some cases, private third-party payors. Although the specific provisions of these laws vary, their scope is
generally broad and there may not be regulations, guidance or court decisions that apply the laws to particular industry
practices. False claims laws prohibit, among other things, individuals or entities from knowingly presenting, or causing to be
presented, information or claims for payment from Medicare, Medicaid, or other third-party payors that are false or
fraudulent. Violations of fraud and abuse laws may be punishable by criminal or civil sanctions, including fines and civil
monetary penalties, and/or exclusion from federal health care programs (including Medicare and Medicaid).
Laws and regulations have been enacted by the federal government and various states to regulate the sales and
marketing practices of pharmaceutical manufacturers with marketed products. The laws and regulations generally limit
financial interactions between manufacturers and health care providers, require disclosure to the government and public of
such interactions and/or require reporting of pricing information or marketing expenditures. Many of these laws and
regulations contain ambiguous requirements or require administrative guidance for implementation.
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Data Privacy and Security Laws
Pharmaceutical companies may be subject to U.S. federal and state health information privacy, security and data
breach notification laws, which may govern the collection, use, disclosure and protection of health-related and other personal
information. State laws may be more stringent, broader in scope or offer greater individual rights with respect to protected
health information, or PHI, than the federal Health Insurance Portability and Accountability Act of 1996, as amended, and its
implementing regulations, which are collectively referred to as HIPAA, and state laws may differ from each other, which may
complicate compliance efforts. Entities that are found to be in violation of HIPAA as the result of a breach of unsecured PHI, a
complaint about privacy practices or an audit by the HHS, may be subject to significant civil, criminal and administrative fines
and penalties and/or additional reporting and oversight obligations if required to enter into a resolution agreement and
corrective action plan with HHS to settle allegations of HIPAA non-compliance.
In addition to federal regulation, many states have begun to focus on efforts to regulate privacy and data security. For
example, in California the California Consumer Privacy Act, or CCPA, which went into effect on January 1, 2020 and was
expanded by the California Consumer Privacy Rights Act, or CPRA, which went into effect on January 1, 2023, collectively
establishes a privacy framework for covered businesses by creating an expanded definition of personal information,
establishing new data privacy rights for consumers in the State of California, imposing special rules on the collection of
consumer data from minors, and creating a new and potentially severe statutory damages framework for violations and for
businesses that fail to implement reasonable security procedures and practices to prevent data breaches. There also are states
that are specifically regulating health information that may affect our business. 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. 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. territories have enacted data breach notification laws. Achieving and sustaining
compliance with applicable international, federal and state privacy, security, and data breach notification laws may prove time-
consuming and costly.
EEA Member States, the United Kingdom, Switzerland and other jurisdictions have also adopted data protection laws
and regulations, which impose significant compliance obligations. In the EEA and the United Kingdom, the collection and use
of personal data, including clinical trial data, is governed by the provisions of the General Data Protection Regulation, or
GDPR. The GDPR, together with national legislation, regulations and guidelines of the EEA Member States, the United
Kingdom and Switzerland governing the processing of personal data, impose strict obligations and restrictions on the ability to
collect, analyze and transfer personal data, including health data from clinical trials and adverse event reporting. In particular,
these obligations and restrictions concern the consent of the individuals to whom the personal data relates, the information
provided to the individuals, the transfer of personal data out of the EEA, the United Kingdom or Switzerland, data breach
notifications, security and confidentiality, responding and handling data subject rights, ensuring appropriate assessments are
carried out on processing operations and documented. Under these laws, data protection authorities can impose substantial
potential fines for breaches of the data protection obligations. European data protection authorities may interpret the GDPR
and national laws differently and impose additional requirements, which add to the complexity of processing personal data in
or from the EEA, United Kingdom or Switzerland.
Human Capital
As of December 31, 2024, we had 253 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. 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. 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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Culture and Development
Fostering a welcoming and inclusive culture is essential to attracting, motivating and retaining the talent necessary to
deliver on our corporate mission. To establish and maintain this culture, we have a simple vision in mind: to make Ironwood
an environment rooted in valuing each employee for who they are.
Our workforce represents the diverse populations we serve and reflects our diversity principles in our employee-
related trainings and policies. Women represent approximately 50% of our employee base, 30% of our leadership team (vice
president and above) and 33% of our board of directors (including our board and audit committee chairs). Additionally,
approximately 20% of our employees are racially or ethnically diverse and in 2024, approximately 20% of our new hires were
racially or ethnically diverse (excluding Europe-based employees, for which race and ethnicity is not disclosed).
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.
Compensation and Benefits
All our employees receive equity and are encouraged to think and act as owners of Ironwood. We strive to provide
pay, benefits, and services that are competitive to market and to create incentives to attract, motivate and retain our employees.
We are focused on pay equity and regularly monitor our pay practices among similar roles and responsibilities throughout our
organization.
Communication and Engagement
We strongly believe that our success depends on employees understanding how their work contributes to our ability
to execute on our vision, mission and strategy. Our communication and engagement efforts seek to offset competitive talent
challenges in the biopharmaceutical industry and employees’ higher expectations of their employers. To this end, we utilize a
variety of channels to facilitate open and direct communication, including frequent town hall meetings, Ironwood intranet,
CEO blog, leadership engagement opportunities, regular communications regarding business updates, and employee
engagement surveys.
Available Information
You may obtain free copies of our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q and Current
Reports on Form 8-K, and amendments to those reports, as soon as reasonably practicable after they are electronically filed or
furnished to the SEC, on the Investors section of our website at www.ironwoodpharma.com or by contacting our Investor
Relations department at 617-374-5230. The contents of our website are not incorporated by reference into this report and you
should not consider information provided on our website to be part of this report.
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PART II OTHER INFORMATION
Item 1A. Risk Factors
In addition to the other information in this Annual Report on Form 10-K, any of the factors described below could
significantly and negatively affect our business, financial condition, results of operations or prospects. The trading price of
our Class A Common Stock may decline due to these risks.
Risks Related to LINZESS, Apraglutide and Other Product Candidates
We are highly dependent on the commercial success of LINZESS (linaclotide) in the U.S. for the foreseeable future.
We and our partner, AbbVie, began selling LINZESS in the U.S. in December 2012. Revenues from our LINZESS
collaboration constitute a significant portion of our total revenue, and we believe they will continue to do so for the
foreseeable future. The commercial success of LINZESS depends on a number of factors, including:
●
the effectiveness of LINZESS as a treatment for adult patients with IBS-C, or CIC, and as a treatment for
pediatric patients aged 6-17 years-old with FC;
●
the size of the treatable patient population;
●
the effectiveness of the sales, managed markets and marketing efforts , including the ability to adapt a
commercial model and market strategy to the evolving landscape;
●
the coverage and reimbursement levels set by governmental authorities, private health insurers and other third-
party payors;
●
the status of government regulation in the life sciences industry, particularly with respect to healthcare reform
and drug pricing;
●
the adoption of LINZESS by physicians, which depends on whether physicians view it as a safe and effective
treatment for adult patients with IBS-C and CIC and pediatric patients ages 6-17 years-old with FC;
●
our success in educating and activating adult IBS-C and CIC patients, and children and adolescents ages 6-17
years-old FC patients and their caregivers, to seek physician care for their symptoms;
●
our ability to both secure and maintain adequate reimbursement for, and optimize patient access to, LINZESS
and our ability to demonstrate that LINZESS is safer, more efficacious and/or more cost-effective than
alternative therapies;
●
the effectiveness of our partners’ distribution networks;
●
the occurrence of any side effects, adverse reactions or misuse, or any unfavorable publicity in these or other
areas, associated with linaclotide; and
●
the development or commercialization of products or therapies that compete with LINZESS.
Our revenues from the commercialization of LINZESS are subject to these and other factors, and therefore has been
and may be unpredictable from quarter-to-quarter and year-to-year.
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We are subject to uncertainty relating to pricing and reimbursement policies in the U.S., including recent and future
healthcare reform measures, which, if not favorable for our products, could hinder or prevent our products’ commercial
success.
Our and our partner’s ability to commercialize our products successfully depends in part on the coverage and
reimbursement levels set by governmental authorities, private health insurers and other third-party payors. In determining
whether to approve reimbursement for our products and at what level, we expect that third-party payors will consider factors
that include the efficacy, cost effectiveness and safety of our products, as well as the availability of other treatments, including
generic prescription drugs and OTC alternatives. Further, in order to obtain and maintain acceptable reimbursement levels and
access for patients at copay levels that are reasonable and customary, we have offered, and expect to continue to face
increasing pressure to offer, discounts or rebates from list prices or discounts to third-party payors or other unfavorable pricing
modifications. Obtaining and maintaining favorable reimbursement can be a time consuming and expensive process, and there
is no guarantee that we or AbbVie, with respect to LINZESS in the U.S., will be able to negotiate or continue to negotiate
pricing terms with third-party payors at levels that are profitable to us, or at all. Certain third-party payors also require prior
authorization for, or have refused to provide, reimbursement for our products, and others may do so in the future. Our business
would be materially adversely affected if we and our partners are not able to receive approval for reimbursement of our
products from third-party payors on a broad, timely or satisfactory basis; or if reimbursement is subject to overly broad or
restrictive prior authorization requirements; or if reimbursement is not maintained at satisfactory levels or becomes subject to
prior authorization. In addition, our business could be adversely affected if government healthcare programs, private health
insurers, including managed care organizations, or other reimbursing bodies or payors limit or reduce the indications for or
conditions under which our products may be reimbursed. Moreover, as discussed further below and above in Part I, Item
1,under the heading Pricing and Reimbursement, changes in insurance coverage or reimbursement levels by governmental
authorities, private health insurers and other third-party payors, or in the type of such coverage held by patients may
materially harm our business and commercialization efforts.
We have experienced and may experience additional pricing pressures in connection with the sale of our current and
future products due to the healthcare reforms discussed below and above in Part I, Item 1,under the heading Pricing and
Reimbursement, as well as the trend toward initiatives aimed at reducing healthcare costs, the increasing influence of managed
care, the scrutiny of pharmaceutical pricing, the ongoing debates on reducing government spending and additional legislative
proposals. There has been significant scrutiny of pharmaceutical pricing and the resulting costs of pharmaceutical products
that could cause significant operational and reimbursement changes for the pharmaceutical industry. There have been a
number of federal and state efforts to address drug costs, which generally have focused on increasing transparency around
drug costs or limiting drug prices, price increases or other related costs. Certain of these efforts have resulted in legislative and
regulatory reforms.
For example, and as discussed further below and above in Part I, Item 1,under the heading Pricing and
Reimbursement, the IRA could have the effect of reducing the net prices for our products and product candidates. As another
example, legislation enacted in 2021 revised the Medicaid drug rebate program in which we and other manufacturers
participate so that Medicaid rebates were no longer capped at 100% of the quarterly average manufacturer price effective
January 1, 2024. We anticipate that legislative and regulatory reforms, including the Medicaid drug rebate program revisions,
may adversely affect our revenues and our ability to maintain satisfactory net prices on our products, including LINZESS.
Healthcare reform and other governmental and private payor initiatives may have an adverse effect upon, and could
prevent, our products’ or product candidates’ commercial success.
The U.S. government and individual states have been aggressively pursuing healthcare reform designed to impact
delivery of, and/or payment for, healthcare, which includes initiatives intended to reduce the cost of healthcare. For example,
in March 2010, the U.S. Congress enacted the PPACA, as modified by the Health Care and Education Reconciliation Act, or
the ACA, which, among other things, expanded healthcare coverage through Medicaid expansion and the implementation of
the individual health insurance mandate; included changes to the coverage and reimbursement of drug products under
government healthcare programs; imposed an annual fee on manufacturers of branded drugs; and expanded government
enforcement authority.
Beyond the ACA, there have been ongoing legislative and administrative and other health care reform efforts, which
could have an adverse effect on our products’ or product candidates’ commercial success. Some healthcare reform
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efforts affect pricing or payment for drug products or the healthcare industry more generally. Drug pricing and payment
reform was a focus of the former Biden Administration and is likely to continue to be a focus of the current Trump
Administration. For example, federal legislation enacted in 2021 eliminated the statutory cap on Medicaid drug rebate
program effective January 1, 2024.
Most significantly, in August 2022, President Biden signed the IRA into law. This statute marks the most significant
action by Congress with respect to the pharmaceutical industry since the adoption of the ACA in 2010. The IRA contains
various drug pricing and payment provisions. Among other provisions, the IRA imposes a yearly cap ($2,000 in 2025) on out-
of-pocket prescription drug prices in Medicare Part D. Additionally, the IRA, through a newly established Manufacturer
Discount Program, eliminated, effective January 1, 2025, the size of the discount on brand-name drugs that pharmaceutical
manufacturers are required to offer Medicare beneficiaries who are in the Medicare Part D coverage gap, or “donut hole,” by
significantly lowering the beneficiary maximum out-of-pocket cost and requiring pharmaceutical manufacturers to provide a
10% discount in the initial coverage phase of the plan and 20% discount in the catastrophic coverage phase of the plan on
brand-name drugs.
In addition, the IRA requires Medicare to negotiate prices for certain high-cost drugs and biologicals, including both
physician-administered products covered under Medicare Part B benefit and self-administered drugs covered under the
Medicare Part D benefit. 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). CMS will publish the negotiated
price, known as the MFP for each of the selected products. Manufacturers of selected drugs would be required to offer the
drug for Medicare recipients at the MFP. 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, 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. Depending on the share of Medicare spending each year that is attributed
to LINZESS or any other product candidate that we develop and whether or not those drugs become eligible for Medicare
negotiation, those drugs and our revenue may be adversely impacted by this provision.
It is unclear how the IRA will be implemented. While there had been some questions about the Trump
Administration’s position on this program, CMS issued a public statement on January 29, 2025, declaring that lowering the
cost of prescription drugs is a top priority of the new administration and CMS is committed to considering opportunities to
bring greater transparency in the negotiation program. On June 6, 2023, Merck & Co. filed a lawsuit against the HHS and
CMS asserting that, among other things, the IRA’s Drug Price Negotiation Program for Medicare constitutes an
uncompensated taking in violation of the Fifth Amendment of the Constitution. Subsequently, a number of other parties,
including the U.S. Chamber of Commerce, also filed lawsuits in various courts with similar constitutional claims against the
HHS and CMS. HHS has generally won the substantive disputes in these cases, and various federal district court judges have
expressed skepticism regarding the merits of the legal arguments being pursued by the pharmaceutical industry. Certain of
these cases are now on appeal and the Court of Appeals for the Third Circuit heard oral argument in three of these cases. We
expect that litigation involving these and other provisions of the IRA will continue, with unpredictable and uncertain results.
Healthcare reform efforts have been and may continue to be subject to scrutiny and legal challenge. For example,
with respect to the ACA, tax reform legislation was enacted that eliminated the tax penalty established for individuals who do
not maintain mandated health insurance coverage beginning in 2019 and, in 2021, the U.S. Supreme Court dismissed the latest
judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA. As
another example, revisions to regulations under the federal anti-kickback statute would remove protection for traditional
Medicare Part D discounts offered by pharmaceutical manufacturers to pharmacy benefit managers and health plans. The
revisions were challenged in court and, pursuant to court order, the removal was delayed, and recent legislation imposed a
moratorium on implementation of the rule until January 2032. Certain pharmaceutical manufacturers and organizations have
filed lawsuits challenging the IRA drug price negotiation program.
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Adoption of new healthcare reform legislation at the federal or state level could negatively affect demand for, or pricing of,
our products or product candidates if approved for sale.
In addition, other legislative changes have been adopted that could have an adverse effect upon, and could prevent,
our products’ or product candidates’ commercial success. For example, the Budget Control Act of 2011, as amended, or the
Budget Control Act, includes provisions intended to reduce the federal deficit, including reductions in Medicare payments to
providers through 2032 (except May 1, 2020 to March 31, 2022). Any significant spending reductions affecting Medicare,
Medicaid or other publicly funded or subsidized health programs, or any significant taxes or fees imposed as part of any
broader deficit reduction effort or legislative replacement to the Budget Control Act, or otherwise, could have an adverse
impact on our anticipated product revenues.
Additionally, in its 2024 decision in Loper Bright Enterprises v. Raimondo, the U.S. Supreme Court overruled the
“Chevron doctrine,” which gives deference to regulatory agencies’ statutory interpretations in litigation against federal
government agencies, such as the U.S. FDA, CMS and other federal agencies where the law is ambiguous. This Supreme
Court decision may lead to challenges of long standing decisions and policies of these agencies, which could lead to
uncertainties in the industry and disrupt the federal agency’s operations.
In addition to governmental efforts in the U.S., foreign jurisdictions as well as private health insurers and managed
care plans are likely to continue challenging manufacturers’ ability to obtain reimbursement, as well as the level of
reimbursement, for pharmaceuticals and other healthcare-related products and services.
We are unable to predict what additional legislation, regulations or policies, if any, relating to the healthcare industry
or third-party coverage and reimbursement may be enacted in the future or what effect such legislation, regulations or policies
would have on our business. Any cost-control initiatives, legislative and administrative or other healthcare system reforms
aimed at controlling and reducing healthcare costs, including through measures designed to limit reimbursement, restrict
access or impose unfavorable pricing modifications on pharmaceutical products, could impact our and our partners’ ability to
obtain or maintain reimbursement for our products at satisfactory levels and could significantly decrease the available
coverage and the price we have or might establish for our products and product candidates, which would have an adverse
effect on our business and financial results.
We must work effectively and collaboratively with AbbVie to market and sell LINZESS in the U.S., and we must adapt our
commercial model and market strategy to the evolving landscape for LINZESS to achieve its maximum commercial
potential.
We are working closely with AbbVie to execute our joint commercialization plan for LINZESS. The
commercialization plan includes an agreed upon marketing campaign that targets the physicians who see patients who could
benefit from LINZESS treatment. LINZESS’s consumer marketing campaign targets the adult men and women who suffer
from IBS-C or CIC.
In order to optimize the commercial potential of LINZESS, we and AbbVie must execute upon this
commercialization plan effectively and efficiently. In addition, we and AbbVie must continually assess, modify and adapt our
commercialization plan in a coordinated and integrated fashion, including evaluating and adjusting as necessary the level and
mix of marketing and promotion efforts, in response to changing business, market or other factors in order to advance the
commercial potential of LINZESS. Further, we and AbbVie must continue to focus the sales and marketing efforts for the
brand on educating customers about the relevant data and information for LINZESS in treating adults with IBS-C and CIC,
and taking a measured approach to educating and raising awareness on the FC indication for pediatric patients ages 6-17
years-old. We and AbbVie must ensure a highly targeted and efficient promotional mix combined to continue effectively
promoting LINZESS to key healthcare professionals. If we and AbbVie fail to evolve with the changing commercial landscape
successfully and perform these commercial functions in the highest quality manner and in accordance with our joint
commercialization plan and related agreements, LINZESS will not achieve its maximum commercial potential and we may
suffer financial harm. Our commercial efforts to further target and engage adult patients with IBS-C or CIC may not
effectively increase appropriate patient awareness or patient/physician dialogue and may not increase the revenues that we
generate from LINZESS.
We cannot give any assurance that apraglutide will receive regulatory approval, which is necessary before it can be
commercialized.
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Upon the closing of the VectivBio Acquisition, we added apraglutide, a next generation, long-acting GLP-2 analog in
development for SBS patients who are dependent on PS, to our pipeline.
Apraglutide will require extensive clinical development, management of nonclinical, clinical and manufacturing
activities, regulatory approval and adequate manufacturing supply, and if approved, fully integrating apraglutide into our
commercial infrastructure to support the appropriate sales, marketing, and market access efforts to generate sales in pursuit of
revenue. 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. We are also conducting an open-label extension study, STARS Extend, to further assess safety of apraglutide in adult
patients with SBS-IF. Based on these results, we have initiated a rolling NDA submission to the U.S. FDA for apraglutide for
the treatment of adult patients with SBS who are dependent on PS. We are not permitted to market or promote this product
candidate before we receive regulatory approval from the U.S. FDA, the EMA, or comparable foreign regulatory authorities in
the applicable jurisdiction, and we may never receive any such regulatory approval for apraglutide. To obtain regulatory
approvals for apraglutide, we must demonstrate with substantial evidence from adequate and well-controlled clinical trials,
and to the satisfaction of the U.S. FDA, EMA or comparable foreign regulatory authorities, that such product candidate is safe
and effective for its intended uses. We may be required by the U.S. FDA, EMA or comparable foreign regulatory authorities to
perform additional or unanticipated clinical trials to obtain regulatory approval. In the event the U.S. FDA were to determine
that the data from our pivotal Phase III clinical trial, STARS, combined with the data from our open-label extension study,
STARS Extend, is insufficient for acceptance of our NDA, or if we need to conduct any other U.S. FDA-required studies,
approval of our any NDA may be delayed or may require us to expend more resources than we have available. It is also
possible that additional studies, if performed and completed, may not be considered sufficient by the U.S. FDA to approve our
NDA. Any delay in obtaining, or an inability to obtain, any marketing approvals would prevent us from commercializing our
product candidates, including apraglutide, generating revenues on such product candidates and achieving and sustaining
profitability. If any of these outcomes occur, we may be forced to abandon our development efforts for our product candidates,
which could significantly and materially harm our business. Even if we do receive such regulatory approval, we may be
unable to successfully commercialize apraglutide within any approved indications or develop apraglutide for the treatment of
additional indications, which would materially adversely impact our business and prospects.
The regulatory approval processes in the U.S., in the E.U. and in other foreign jurisdictions are onerous, lengthy, time
consuming, expensive and inherently unpredictable. If we are ultimately unable to obtain regulatory approval for
apraglutide or our other product candidates, our business will be harmed.
The time required to complete drug development and to obtain regulatory approval from the U.S. FDA, EMA and
other comparable foreign regulatory authorities is unpredictable, typically takes many years following the commencement of
clinical trials and depends upon numerous factors. In addition, regulatory approval policies, regulations, or the type and
amount of clinical data necessary to gain regulatory approval may change during the course of a product candidate’s clinical
development and may vary among jurisdictions, which may cause delays in the regulatory approval of or may result in the
decision not to approve apraglutide or other product candidates. Regulatory approval is never guaranteed. Data obtained from
nonclinical studies and clinical trials are susceptible to varying interpretations, and regulatory authorities may not interpret our
data as favorably as we do, which may further delay, limit or prevent development efforts, clinical trials, or regulatory
approval. Even if we believe the nonclinical or clinical data for our product candidates are sufficient to support approval, such
data may not be considered sufficient to support approval by the U.S. FDA, EMA and other comparable foreign regulatory
authorities. As an example, in December 2024, the U.S. FDA issued Zealand, which is developing glepaglutide, a long-acting
GLP-2 analog, for the potential treatment of SBS for patients who are dependent on PS, a Complete Response Letter
concluding that glepaglutide did not meet the full requirements for substantial evidence to establish efficacy and safety and
recommended conducting an additional clinical trial to provide further data. Consequently, Zealand now is expecting to
initiate an additional Phase III clinical trial in 2025. Of the large number of drugs in development, only a small percentage
successfully complete the U.S. FDA, EMA or comparable foreign regulatory approval processes and are commercialized.
Accordingly, it is possible that we will never obtain regulatory approval, or that regulatory approval may be substantially
delayed, for apraglutide or our other product candidates.
The U.S. FDA, EMA or other foreign comparable regulatory authorities may delay, limit, or deny approval of our
product candidates, including apraglutide, for many reasons, including the following:
●
the U.S. FDA, EMA or other comparable foreign regulatory authorities may disagree with the design or
implementation of our clinical trials or with our interpretation of data from preclinical studies or clinical
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trials;
●
the population studied in the clinical program may not be sufficiently broad or representative to assure
safety or efficacy in the full population for which we seek approval;
●
the data collected from our clinical trials may not be sufficient to support the submission of an NDA, MMA,
or other submission or to obtain regulatory approval in the U.S., Europe or elsewhere;
●
participants in our clinical trials or individuals using drugs similar to our product candidates may experience
serious and unexpected drug-related side effects;
●
we may be unable to demonstrate to the U.S. FDA, EMA or other comparable foreign regulatory authorities
that a product candidate’s risk-to-benefit ratio for its proposed indications is acceptable;
●
the U.S. FDA, EMA or other comparable foreign regulatory authorities may disagree regarding the
formulation, labeling and/or the specifications of a product candidate;
●
the U.S. FDA, EMA or other comparable foreign regulatory authorities may fail to approve the
manufacturing processes, test procedures and specifications, or facilities of third-party manufacturers with
which we contract for clinical and commercial supplies; and
●
the regulatory approval policies or regulations of the U.S. FDA, EMA, or other applicable comparable
foreign regulations in the E.U. and other jurisdictions may significantly change in a manner rendering our
clinical data insufficient for approval.
In addition, apraglutide may also be regulated as a drug and device combination product by the U.S. FDA, EMA and
comparable foreign regulatory authorities. Developing and obtaining regulatory approval for combination products can pose
unique challenges because they involve components that are regulated under different types of regulatory requirements and
potentially by different U.S. FDA centers or regulatory authorities. As a result, combination product candidates may raise
regulatory, policy and review challenges. Differences in regulatory pathways for each component of a combination product
can impact the regulatory processes for all aspects of product development and management, including clinical investigations,
marketing applications, manufacturing and quality control, adverse event reporting, promotion and advertising, user fees and
post-approval modifications. Although the U.S. FDA, EMA, and comparable foreign authorities have systems in place for the
review and approval of combination products, we may experience additional delays in the development and
commercialization of apraglutide due to regulatory timing constraints and uncertainties in the product development and
approval process. Moreover, although we expect that the device component would be reviewed in connection with the review
of the drug marketing application for apraglutide, if and when submitted, and that no separate marketing authorization or
certification for the device component will be required, the U.S. FDA, EMA or comparable regulatory authorities may
disagree and require that we obtain a separate marketing authorization or certification for the device component, which could
further delay or prevent regulatory approval of apraglutide.
This lengthy drug development and regulatory approval process, as well as the unpredictability of the results of
clinical trials, may result in our failure to obtain regulatory approval to potentially market apraglutide or our other product
candidates, which would significantly harm our business, results of operations, and prospects.
Our failure to successfully develop and commercialize additional product candidates or approved products would impair
our ability to grow and/or adversely affect our business.
As part of our growth strategy, we intend to explore further linaclotide development opportunities as well as to
advance the development of our other pipeline programs, such as apraglutide, through internal or external opportunities.
We and AbbVie are exploring development opportunities to enhance the clinical profile of LINZESS by studying
linaclotide in new or existing indications, populations and formulations to assess its potential to treat various conditions. For
example, we and AbbVie have established a nonclinical and clinical post-marketing plan with the U.S. FDA to understand the
safety and efficacy of LINZESS in pediatric patients. In June 2023, the U.S. FDA approved LINZESS, and in September
2024, Health Canada approved CONSTELLA, as once-daily treatments for pediatric patients ages 6-17 years-old with FC, in
the U.S. and Canada, respectively. Additional clinical pediatric programs in IBS-C and FC are ongoing. These development
efforts may fail or may not increase the revenues that we generate from LINZESS. Furthermore, they may result in adverse
events, or perceived adverse events, in certain patient populations that are then attributed to the currently approved patient
population, which may result in adverse regulatory action at the
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U.S. FDA or in other countries or harm linaclotide’s reputation in the marketplace, each of which could materially harm our
revenues from linaclotide.
The strength of our company’s pipeline will depend in large part on the outcomes of studies and regulatory approvals
of assets in our pipeline, such as apraglutide, and any other assets that we may acquire or license from third parties. Through
the VectivBio Acquisition, we added apraglutide to our 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. We are also conducting open-label extension studies to further
evaluate the efficacy, safety and tolerability of apraglutide in SBS-IF and to support potential submissions of marketing
applications for apraglutide in the U.S., European Union, or E.U., and Japan. Based on the STARS Phase III clinical trial
results and data analyzed from the open-label extension studies, we initiated a rolling NDA submission to the U.S. FDA for
apraglutide for the treatment of adult patients with SBS who are dependent on PS.
We may spend several years and make significant investments in developing any current or future product candidate,
and failure may occur at any point. Our product candidates must satisfy rigorous standards of safety and efficacy before they
can be approved for sale by the U.S. FDA, EMA or comparable foreign authorities. To satisfy these standards, we must
allocate resources among development programs and we must engage in costly and lengthy research and development efforts,
which are subject to unanticipated delays and other significant uncertainties. Despite our efforts, our product candidates may
not offer therapeutic or other improvement over existing competitive drugs, be proven safe and effective in clinical trials, or
meet applicable regulatory standards. It is possible that none of the product candidates we develop will be approved for
commercial sale, which would impair our ability to grow.
We have ongoing or planned nonclinical studies and clinical trials for linaclotide and apraglutide. Many companies in
the pharmaceutical industry have suffered significant setbacks in clinical trials even after achieving promising results in earlier
nonclinical studies or clinical trials. Findings from ongoing or completed nonclinical studies may not be replicated in later
clinical trials or further data analyses, and findings from early-stage clinical trials may not be predictive of the results we may
obtain in later-stage clinical trials or of the likelihood of regulatory approval. A failure of one or more clinical trials can occur
at any stage of testing, which may result from a multitude of factors, including, among other things, flaws in study design or
implementation, dose selection issues, placebo effects, patient enrollment criteria and failure to demonstrate favorable safety
or efficacy traits. Results from clinical trials and findings from nonclinical studies could lead to abrupt changes in
development activities, including the possible limitation or cessation of development activities associated with a particular
product candidate or program. We cannot be certain that linaclotide or apraglutide will be successful in ongoing, planned or
future clinical trials. Furthermore, our analysis of data obtained from nonclinical and clinical activities is subject to
confirmation and interpretation by the U.S. FDA, EMA and other applicable regulatory authorities, which could delay, limit or
prevent regulatory approval. The U.S. FDA, EMA or other regulatory authorities may also require additional clinical trials,
which may be costly or delay, limit, prevent or otherwise impact regulatory submission or approval. Satisfaction of U.S. FDA,
EMA or other applicable regulatory requirements is costly, time-consuming, uncertain and subject to unanticipated delays. We
cannot give any assurance that apraglutide or our other product candidates will receive regulatory approval. Even if we do
receive such regulatory approval, we may be unable to successfully commercialize apraglutide or any other product candidate
in any approved indications or develop such product candidates for the treatment of additional indications, which would
materially adversely impact our business and prospects.
Delays in the completion of clinical testing of any of our products or product candidates could result in increased costs and
delay or limit our ability to generate revenues.
Delays in the completion of clinical testing could significantly affect our product development costs and timing of
data readouts and regulatory submissions and potential approvals. We do not know whether planned clinical trials will be
completed on schedule, if at all. The commencement and completion of clinical trials can be delayed for a number of reasons,
including delays related to:
●
obtaining regulatory authorization to commence a clinical trial;
●
reaching agreement on acceptable terms with prospective contract research organizations, or CROs, and
trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among
different CROs and trial sites;
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●
manufacturing sufficient quantities of a product candidate for use in clinical trials;
●
obtaining institutional review board or ethics committee approval to conduct a clinical trial at a prospective
site;
●
recruiting and enrolling patients to participate in clinical trials for a variety of reasons, including
competition from other clinical trial programs for the treatment of similar conditions; and
●
maintaining patients who have initiated a clinical trial but may be prone to withdraw due to side effects
from the therapy, lack of efficacy or personal issues, or who are lost to further follow-up.
Additionally, changes in regulatory requirements and guidance may occur, and we may need or otherwise determine
to amend clinical trial protocols to reflect these changes. Each protocol amendment would require institutional review board
or ethics committee review and approval, which may adversely impact the costs, timing or successful completion of the
associated clinical trials. If we or our partners terminate or experience delays in the completion of any clinical trials, the
commercial prospects for our products or product candidates may be harmed, and our ability to generate product revenues will
be delayed. In addition, many of the factors that cause, or lead to, a delay in the commencement or completion of clinical trials
may also ultimately lead to the denial of regulatory approval.
The pricing of apraglutide and our other product candidates, if and when approved for marketing, will depend in part on
pricing and reimbursement strategies adopted by our competitors.
The pricing of apraglutide and our other product candidates, if and when approved for marketing, will depend, in
part, on the pricing and reimbursement strategies adopted by our competitors. For example, with respect to apraglutide, a
marketed GLP-2 product already exists in the U.S., E.U. and other international markets, which may or may not be
genericized within the coming years. Additionally, it is possible that another investigational GLP-2 may be approved and
launched in advance of the potential approval of apraglutide in the U.S., EMA and Japan. Order of market entry and
reimbursement decisions could place apraglutide at a competitive disadvantage, possibly deny market exclusivity rights,
and/or elevate the need for significant clinical differentiation to support certain pricing decisions. If these or other factors
impact the price we can charge for apraglutide, we may reduce our revenue and results of operations could be affected. Similar
competitive factors could apply to pricing and reimbursement decisions for our other product candidates, if approved, in the
future.
We face competition and new products may emerge that provide different or better alternatives for treatment of the
conditions that our products are approved to treat.
The pharmaceutical industry and the markets in which we operate are intensely competitive. We compete in the
marketing and sale of our products, the development of new products or product candidates and the acquisition of rights to
new products with commercial potential. Certain of our competitors have substantially greater financial, technical and human
resources than us. Mergers and acquisitions in the pharmaceutical industry may result in even more resources being
concentrated in our competitors and enable them to compete more effectively. Competition may also increase further as a
result of advances made in the commercial applicability of technologies and greater availability of capital for investment in
these fields. Additionally, new developments, including the development of other drug technologies and methods of
preventing the incidence of disease, occur in the pharmaceutical and medical technology industries at a rapid pace. These
developments may render our products obsolete or noncompetitive.
Linaclotide competes with certain prescription therapies and OTC products, some of which have attained significant
levels of market acceptance. The availability of prescription competitors and OTC products could limit the demand, and the
price we are able to charge, for LINZESS unless we are able to maintain market acceptance among the medical community
and patients and differentiate LINZESS on the basis of actual or perceived clinical benefits supported by broad payer access.
For example, Takeda’s AMITIZA (lubiprostone) is approved by the U.S. FDA for sale in the U.S. for the treatment of IBS-C,
CIC and opioid-induced constipation; Bausch’s TRULANCE (plecanatide) is approved by the U.S. FDA for sale in the U.S.
for the treatment of adults with IBS-C and CIC; Takeda’s MOTEGRITY (prucalopride) is approved by the U.S. FDA for the
treatment of CIC in adults; Ardelyx’s IBSRELA™ (tenapanor) is approved by the U.S. FDA for the treatment for IBS-C in
adults; and Vibrant Gastro Inc.’s Vibrant, a drug-free capsule, is approved by the U.S. FDA for the treatment of CIC in adults
who have not experienced relief of their bowel symptoms by using laxative therapies at the recommended dosage for at least
one month. OTC laxatives such as MiraLAX® and DULCOLAX®, and lactulose, a prescription laxative treatment, are also
available for the treatment of constipation. Additionally, we believe other companies are developing products that could
compete with linaclotide, should they be
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approved by the U.S. FDA or comparable foreign regulatory authorities and become commercially available. In addition, there
are other compounds in late-stage development and other potential competitors that are in earlier stages of development that, if
approved, may compete with linaclotide. If our current or potential competitors are successful in completing drug
development for their drug candidates and obtain approval from the U.S. FDA or comparable foreign regulatory authorities,
they could limit the demand for linaclotide. In addition to competition from such prescription and OTC products, we may also
face competition from multiple low-cost generic versions of such products when available in the U.S. For example, an
authorized generic version of AMITIZA was first launched in the U.S. in January of 2021 and multiple versions are now
available. It is possible that additional generic versions may become available in the future.
In addition, any product candidates that we successfully develop and commercialize will compete with existing drugs
and new drugs that may become available in the future. Apraglutide, if successfully developed and approved, will 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, which is developing glepaglutide, a long-acting GLP-2 analog, for the treatment of SBS for patients who are
dependent on PS and is expecting to initiate an additional Phase III clinical trial in 2025. Hanmi Pharmaceutical is also
developing a GLP-2 analog, to be administered once a month, and which is in a Phase II clinical trial. Products with other
mechanisms of action may emerge as future competition.
Our products or product candidates may cause undesirable side effects or have other properties that could delay or prevent
their development, create unpredictable clinical trial results, impact its regulatory approval or limit their commercial
potential.
Undesirable side effects caused by our products or product candidates, including adverse events associated with our
product candidates, could cause us or regulatory authorities to interrupt, delay or halt clinical trials and could result in a more
restrictive label or the delay or denial of regulatory approval by the U.S. FDA, EMA or other comparable foreign regulatory
authorities. Additionally, with respect to our approved products, as patient experience increases and expands, or if one or more
of our product candidates receives marketing approval, we, our partners, or others may later identify previously unknown side
effects, known side effects may be found to be more frequent and/or severe than in the past, or detect unexpected safety
signals for our products or any products perceived to be similar to our products. The foregoing, or the perception of the
foregoing, may have the following effects, among others:
●
sales of our products may be impaired;
●
regulatory approvals for our products may be delayed, denied, restricted or withdrawn;
●
we or our partners may decide to, or be required to, change the products’ labeling or send product warning
letters or field alerts to physicians, pharmacists or hospitals;
●
reformulation of the products, additional nonclinical studies or clinical trials, changes in labeling or
changes to or re-approvals of manufacturing facilities may be required;
●
we or our partners may be precluded from pursuing approval of our products in new territories or from
studying additional development opportunities to enhance our products’ clinical profiles, including within
new or existing indications, populations or formulations, as well as in potential combination products;
●
we may be required to create a Risk Evaluation and Mitigation Strategy, or REMS, plan, or similar actions
in other jurisdictions which could include a medication guide outlining the risks of such side effects for
distribution to patients, a communication plan for healthcare providers or other elements to assure safe
use;
●
our or our products’ reputation in the marketplace may suffer; and
●
government investigations or lawsuits, including class action suits, may be brought against us or our
partners.
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Any of the above occurrences could prevent us from achieving or maintaining market acceptance of our product
candidates, if they are approved, and could significantly harm our business, results of operations, and prospects, prevent sales
of our products, increase expenses and impair our and our partners’ ability to successfully commercialize our products.
Linaclotide has been prescribed to millions of patients since its launch in the U.S. and other territories beginning in
December 2012. The number and type of patients treated with linaclotide could continue to grow if physicians prescribe
linaclotide to more patients and as we and our partners conduct clinical trials, including in new indications, populations or
formulations, as well as explore potential combination products, in existing and new territories. As the patient experience with
linaclotide increases and expands, we and others may identify previously unknown side effects, known side effects may be
found to be more frequent or severe than in the past, and others may detect unexpected safety signals for linaclotide or any
products perceived to be similar to linaclotide. The most commonly reported adverse reaction since linaclotide became
commercially available, as well as in the clinical trials for linaclotide in IBS-C and CIC, has been diarrhea. In the linaclotide
Phase III IBS-C and CIC trials in adults, severe diarrhea was reported in 2% or less of the linaclotide-treated patients and its
incidence was similar between the IBS-C and CIC populations. In the linaclotide Phase III FC trial in pediatric patients ages 6-
17 years-old, severe diarrhea was reported in one linaclotide-treated patient.
In addition, the U.S. FDA-approved labeling for LINZESS contains a boxed warning describing the risk of serious
dehydration in pediatric patients less than two years of age and a contraindication against its use in these patients. These and
other restrictions could limit the commercial potential of LINZESS. We and AbbVie have established a nonclinical and
clinical post-marketing plan with the U.S. FDA to understand the safety and efficacy of LINZESS in pediatric patients. In
June 2023, the U.S. FDA approved LINZESS as a once-daily oral 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. There can be no assurances,
however, whether there may be any significant unknown side effects that could limit the commercial potential of LINZESS in
this pediatric population.
Patients treated with apraglutide may experience well-known class-specific adverse events. The most frequently
adverse events in our pivotal Phase III clinical trial, STARS, were abdominal pain, nasopharyngitis, nausea, headache, rash,
and fatigue. There may be additional mechanistic side effects that are only observed in future clinical trials and/or through
real-world experience with patients using our products.
Even though LINZESS is approved by the U.S. FDA for use in adult and certain pediatric patients, post-approval
development and regulatory requirements still remain, which may present additional challenges, and we may not be
successful in obtaining approval for additional indications for LINZESS that we are seeking or may seek in the future.
In August 2012, the U.S. FDA approved LINZESS as a once-daily treatment for adult men and women suffering
from IBS-C or CIC. Although we and AbbVie completed additional nonclinical studies and clinical trials in adults that were
required by the U.S. FDA in connection with the approval of LINZESS, LINZESS remains subject to ongoing U.S. FDA
requirements, including those governing the testing, manufacturing, labeling, packaging, storage, advertising, promotion, sale,
distribution, recordkeeping and submission of safety and other post-market information. For example, the U.S. FDA has the
authority to require post-marketing studies and clinical trials, labeling changes based on new safety information, and
compliance with REMS approved by the U.S. FDA.
The U.S. FDA-approved labeling for LINZESS contains a boxed warning describing the risk of serious dehydration
in pediatric patients less than two years of age and a contraindication against its use in these patients. We and AbbVie have
established a nonclinical and clinical post-marketing plan with the U.S. FDA to understand the safety and efficacy of
LINZESS in pediatric patients. 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 in support of post-approval requirements. Our ability to expand the indication or labeling information for LINZESS
will depend on, among other things, our successful completion of pediatric clinical programs.
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These post-approval requirements impose resource and cost burdens on us. Failure to effectively, appropriately and
timely conduct and complete the required studies relating to our products, monitor and report adverse events and meet our
other post-approval commitments would lead to negative regulatory action at the U.S. FDA, which could include restrictions
on the sale of our products or withdrawal of regulatory approval of our products for their currently approved indications and
patient populations.
We and our linaclotide partners are subject to uncertainty relating to pricing and reimbursement policies outside the U.S.,
as well as risks relating to the improper importation of linaclotide and sale of counterfeit versions of linaclotide. If such
policies are not favorable, or if linaclotide is improperly imported or is counterfeited, our business and financial results
could be adversely affected.
In some foreign countries, particularly Canada, the countries of Europe, Japan and China, the pricing and payment of
prescription pharmaceuticals are subject to governmental control. In these countries, pricing negotiations with governmental
authorities can take 6 to 12 months or longer after the receipt of regulatory approval and product launch. Reimbursement
sources are different in each country, and each country may include a combination of distinct potential payors, including
private insurance and governmental payors. Some countries may restrict the range of medicinal products for which their
national health insurance systems provide reimbursement and control the prices of medicinal products for human use. To
obtain favorable reimbursement for the indications sought or pricing approval in some countries, we and our partners may be
required to conduct a clinical trial that compares the cost and clinical effectiveness of linaclotide to other available therapies.
Further, several countries have implemented government measures to either freeze or reduce pricing of pharmaceutical
products. Many third-party payors and governmental authorities also consider the price for which the same product is being
sold in other countries to determine their own pricing and reimbursement strategy, so if linaclotide is priced low or gets
limited reimbursement in a particular country, this could result in similarly low pricing and reimbursement in other countries.
If reimbursement for linaclotide is unavailable in any country in which reimbursement is sought, limited in scope or amount,
or if pricing is set at or reduced to unsatisfactory levels, our and our partners’ ability to successfully commercialize linaclotide
in such country would be impacted negatively. Furthermore, if these measures prevent us or any of our partners from selling
linaclotide on a profitable basis in a particular country, they could prevent the commercial launch or continued sale of
linaclotide in that country.
CONSTELLA was first launched in certain European countries for the symptomatic treatment of moderate to severe
IBS-C in adults in the second quarter of 2013 and our partner, AbbVie, is currently commercializing CONSTELLA in a
number of European countries and in Canada. LINZESS was first launched in Japan for the treatment of IBS-C in adults in the
first quarter of 2017, and for the treatment of chronic constipation in adults in the third quarter of 2018, and our partner
Astellas is currently commercializing LINZESS in Japan. In addition, LINZESS was first launched in China for the treatment
of IBS-C in adults in November 2019, and our partner AstraZeneca, is currently commercializing LINZESS in China
(including Hong Kong and Macau). The pricing and reimbursement strategy is a key component of our partners’
commercialization plans for CONSTELLA in Europe and Canada and LINZESS in Japan and China. Our revenues may suffer
if our partners are unable to successfully and timely conclude reimbursement, price approval or funding processes and market
CONSTELLA in key member states of the E.U. and Canada or LINZESS in Japan or China, or if coverage and reimbursement
for either CONSTELLA or LINZESS is limited or reduced. If our partners are not able to obtain or maintain coverage, pricing
or reimbursement on acceptable terms or at all, or if such terms change in any countries in its territory, our partners may not be
able to, or may decide not to, sell either CONSTELLA or LINZESS in such countries.
We and our partners also face the risk that linaclotide is imported or reimported into markets with relatively higher
prices from markets with relatively lower prices, which would result in a decrease of sales and any payments we receive from
the affected market. Additionally, third parties may illegally produce, distribute and/or sell counterfeit or otherwise unfit or
adulterated versions of linaclotide. In either case, we and our partners may not be able to detect or, if detected, prevent or
prohibit the sale of such products, which could result in dangerous health consequences for patients, loss of confidence in us,
our partners and our products, and adverse regulatory or legal consequences. Any of the foregoing or other consequences
could adversely impact our reputation, financial results and business.
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Even though linaclotide is approved for marketing in the U.S. and in a number of other countries, we or our partners may
never receive approval to commercialize linaclotide in additional parts of the world.
In order to market any products outside of the countries where linaclotide is currently approved, we or our partners
must comply with numerous and varying regulatory requirements of other jurisdictions regarding, among other things, safety
and efficacy. Approval procedures vary among jurisdictions and can involve product testing and administrative review periods
different from, and greater than, those in the U.S. and the other countries where linaclotide is approved. Potential risks include
that the regulatory authorities:
●
may not deem linaclotide safe and effective;
●
may not find the data from nonclinical studies and clinical trials sufficient to support approval;
●
may not approve of manufacturing processes and facilities;
●
may not approve linaclotide for any or all indications or patient populations for which approval is sought;
●
may require significant warnings or restrictions on use to the product labeling for linaclotide; or
●
may change their approval policies or adopt new regulations.
If any of the foregoing were to occur, our or our partners’ receipt of regulatory approval in the applicable jurisdiction
could be delayed or we or our partners may never receive approval at all. Further, regulatory approval in one jurisdiction does
not ensure regulatory approval in another, but a failure or delay in obtaining regulatory approval in one jurisdiction may have
a negative effect on the regulatory processes in others. If linaclotide is not approved for all indications or patient populations
or with the labeling requested, this would limit the uses of linaclotide and have an adverse effect on its commercial potential
or require costly post-marketing studies.
Risks Related to Our Growth Strategy
If we are unable to execute on our strategy to in-license or acquire externally developed products or product candidates, or
engage in other transactions with value creation potential, our business and prospects would be materially adversely
affected.
Our future success is largely dependent on our ability to successfully execute on our growth strategy, which includes
in-licensing or otherwise acquiring the rights to externally developed GI or rare diseases products or product candidates or
engaging in other transactions with value creation potential. The success of this strategy depends upon our ability to identify,
select and acquire promising assets, platforms or other opportunities. For example, through the VectivBio Acquisition, we
added apraglutide to our pipeline. There is no assurance that apraglutide will receive regulatory approval.
In addition, the process of proposing, negotiating and implementing a license or acquisition is lengthy and complex
and there is no assurance we will be able to enter into similar transactions in the future. Pursuit of external opportunities is
also a highly competitive area and a number of other companies, including some with substantially greater financial,
development, marketing and sales resources, may compete with us for license or acquisition opportunities. We have limited
resources to identify and execute the acquisition or in-licensing of third-party products, product candidates, businesses or
technologies and integrate them into our current infrastructure. Moreover, we expect to incur a variety of costs and devote
resources to potential acquisitions or in-licensing opportunities that are never completed, or we may fail to realize the
anticipated benefits of such efforts. If we are unable to successfully acquire the rights to additional products or product
candidates on terms that we find acceptable, or at all, or execute other value creating transactions, we will remain smaller, less
diversified and highly dependent on the commercial success of LINZESS and apraglutide, if approved, and our business and
prospects would be materially and adversely affected.
In addition, such in-licenses, acquisitions or other transactions may entail numerous operational and financial risks,
including:
●
development, regulatory and commercialization challenges;
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●
exposure to unknown liabilities;
●
disruption of our business and diversion of our management’s time and attention to develop acquired products,
product candidates, businesses or technologies;
●
incurrence of substantial debt, dilutive issuances of securities or depletion of cash to pay for acquisitions;
●
higher than expected acquisition and integration costs;
●
difficulty in combining the operations and personnel of any acquired businesses with our operations and
personnel;
●
increased amortization expenses;
●
impairment of relationships with key suppliers or customers of any acquired businesses due to changes in
management and ownership; and
●
inability to motivate key employees of any acquired businesses.
The development of product candidates in particular is a highly uncertain process. Any product candidate that we in-
license or acquire may require additional development efforts prior to and after commercial sale, including extensive clinical
testing and approval by the U.S. FDA, EMA and other comparable foreign regulatory authorities. We may also rely on our
licensors and collaboration partners to conduct development activities for certain of our product candidates, and while we may
have oversight of such development activities, such licensees or collaboration partners may not effectively develop any such
product candidates. All product candidates are prone to risks of failure typical of pharmaceutical product development,
including the possibility that a product candidate will not be shown to be sufficiently safe and effective for approval by
regulatory authorities or competitors may develop alternatives that render our potential product candidates obsolete or less
attractive. It is possible that none of the product candidates we may in-license or acquire will be approved for commercial sale
or be otherwise commercially viable, which would impair our ability to grow. Furthermore, we may have little or no insight or
control over the development and commercialization of any product that we in-license outside the licensed territory. If other
licensees do not effectively develop or commercialize any such product outside the licensed territory, our reputation or the
reputation of any such product may be impacted.
If we are unable to successfully partner with other companies to develop and commercialize products and/or product
candidates, our ability to grow would be impaired and our business would be adversely affected.
As part of our business strategy, we may partner with pharmaceutical, biotechnology or other companies to develop
and commercialize products or product candidates. Although we have entered into such arrangements with respect to the
development and commercialization of linaclotide worldwide and of apraglutide in Japan, there can be no assurance that we
will be able to do so in the future with respect to other products or product candidates that we either develop internally or in-
license or that we will be able to gain the interest of potential partners; establish and maintain development, manufacturing,
marketing, sales or distribution relationships on acceptable terms; that such relationships, if established, will be successful or
on favorable terms; or that we will gain market acceptance for such products or product candidates. The process of proposing,
negotiating and implementing a partnership arrangement is lengthy and complex. If we enter into any partnering arrangements
with third parties, any revenues we receive will depend upon the efforts of such third parties. If we are unable to establish
successful partnering arrangements when advantageous, we may not gain access to the financial resources and industry
experience necessary to develop, commercialize or successfully market our products or product candidates, may be forced to
curtail, delay or stop a development program or one or more of our other development programs, delay commercialization,
reduce the scope of our planned sales or marketing activities or undertake development or commercialization activities at our
own expense, and therefore may be unable to generate revenue from products or product candidates or do so to their full
potential.
Risks Related to the VectivBio Acquisition
We may be unable to successfully integrate the business and personnel of VectivBio, and may not realize the expected
benefits and anticipated synergies of such acquisition.
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In December 2023, we completed the VectivBio Acquisition. We may not realize the expected benefits from such
acquisition because of integration difficulties or other challenges.
The success of the VectivBio Acquisition will depend, in part, on our ability to realize all or some of the expected
benefits from the acquisition and anticipated synergies from integrating its business with our existing business. The integration
process may be complex, costly and time-consuming and we may not ultimately realize the return on our investment. Risks we
may face in connection with the VectivBio Acquisition include, among others:
●
failure to successfully implement our business plans for the combined business, including the development of
apraglutide for SBS patients who are dependent on PS;
●
failure of the VectivBio Acquisition to further our business strategy as we expected, including the
commercialization of apraglutide, if approved, for SBS patients who are dependent on PS;
●
unexpected losses of key employees, customers or suppliers, and the complexities associated with integrating
personnel from another company;
●
unanticipated issues in conforming VectivBio’s standards, processes, procedures and controls with our
operations;
●
coordinating product candidate and process development;
●
increasing the scope, geographic diversity and complexity of our operations;
●
diversion of management’s attention from other business concerns;
●
adverse effects on our or VectivBio’s existing business relationships;
●
unanticipated changes in applicable laws and regulations;
●
unanticipated expenses and liabilities associated with the VectivBio Acquisition; and
●
other difficulties in the assimilation of VectivBio operations, technologies, product candidates and systems.
We may have unanticipated or larger than anticipated liabilities for patent and trademark infringement claims,
violations of laws, commercial disputes, taxes and other known and unknown types of liabilities. There may be liabilities that
we underestimated or did not discover in the course of performing our due diligence investigation.
If we experience difficulties with the integration process or if the business of VectivBio deteriorates, the anticipated
benefits, cost savings, growth opportunities and other synergies of the VectivBio Acquisition may not be realized fully or at
all, or may take longer to realize than expected. If any of the above risks occur, our business, financial condition, results of
operations and cash flows may be materially and adversely impacted, we may fail to meet the expectations of investors or
analysts, and our stock price may decline as a result.
Risks Related to Our Dependence on Third Parties
Because we work with partners to develop, manufacture and commercialize linaclotide, we and our partners are dependent
upon third parties, and our and our partners’ relationships with those third parties, in our and our partners’ efforts to
obtain regulatory approval for, and to commercialize, linaclotide, as well as to comply with regulatory and other
obligations with respect to linaclotide.
AbbVie played a significant role in the conduct of the clinical trials for linaclotide and in the subsequent collection
and analysis of data, and AbbVie holds the NDA for LINZESS. AbbVie also continues to play a significant role in the conduct
of our pediatric program for linaclotide. In addition, we are commercializing LINZESS in the U.S. with AbbVie. AbbVie is
also responsible for the development, regulatory approval and commercialization of linaclotide in countries worldwide other
than Japan and China (including Hong Kong and Macau). AbbVie is commercializing
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LINZESS in Mexico and CONSTELLA in Canada as well as in certain countries including in Europe. Astellas and
AstraZeneca are responsible for development and commercialization of LINZESS in Japan and China (including Hong Kong
and Macau), respectively. Each of our partners for linaclotide also is responsible for active pharmaceutical ingredient, or API,
finished drug product and finished goods manufacturing (including bottling and packaging) for its respective territories and
distributing the finished goods to wholesalers. We and/or our partners have commercial supply agreements with independent
third parties to manufacture the linaclotide API.
The integration of our efforts with our partners’ efforts is subject to the uncertainty of the markets for pharmaceutical
products in each partner’s respective territories, and accordingly, these relationships must evolve to meet any new challenges
that arise in those regions. These integrated functions may not be carried out effectively and efficiently if we fail to
communicate and coordinate with our linaclotide partners, and vice versa. Our linaclotide partnering strategy imposes
obligations, risks and operational requirements on us as the central node in our global network of partners. If we do not
effectively communicate with each partner and ensure that the entire network is making integrated and cohesive decisions
focused on the global brand for linaclotide, linaclotide will not achieve its maximum commercial potential. Further, we have
limited ability to control the amount or timing of resources that our partners devote to linaclotide. If any of our partners fails to
devote sufficient time and resources to linaclotide, or if its performance is substandard or otherwise hindered, it will delay the
potential submission or approval of regulatory applications for linaclotide, as well as the manufacturing and
commercialization of linaclotide in the particular territory. A material breach by any of our partners of our collaboration or
license agreement with such partner, or a significant disagreement between us and a partner, could also delay the regulatory
approval and commercialization of linaclotide, potentially lead to costly litigation, and could have a material adverse impact
on our financial condition. Moreover, although we have non-compete restrictions in place with each of our linaclotide
partners, they may have competitive products or relationships with other commercial entities, some of which may compete
with us. If any of our partners competes with us or assists our competitors, it could harm our competitive position.
In addition, adverse event reporting requires significant coordination with our partners and third parties. We are the
holder of the global safety database for linaclotide responsible for coordinating the safety surveillance and adverse event
reporting efforts worldwide with respect to linaclotide; each of Astellas, AstraZeneca and AbbVie is responsible for reporting
adverse event information from its territory to us. If we fail to perform such activities and maintain the global safety database
for linaclotide or if our partners do not report adverse events related to linaclotide, or fail to do so in a timely manner, we may
not receive the information that we or our partners are required to report to the U.S. FDA or a comparable foreign regulatory
authority regarding such products. Furthermore, we or our partners may fail to adequately monitor, identify or investigate
adverse events, or to report adverse events to the U.S. FDA or a comparable foreign regulatory authority accurately and within
the prescribed timeframe. If we or our partners are unsuccessful in any of the foregoing due to poor process, execution,
systems, oversight, communication, adjudication or otherwise, then we may suffer any number of consequences, including the
imposition of additional restrictions on the use of linaclotide, removal of linaclotide from the market, criminal prosecution, the
imposition of civil monetary penalties, seizure of such products, or delay in approval of future products.
We rely entirely on contract manufacturers, our partners and other third parties to manufacture linaclotide, apraglutide,
and our other product candidates and to distribute linaclotide. If they are unable to comply with applicable regulatory
requirements, unable to source sufficient raw materials, experience manufacturing or distribution difficulties, or are
otherwise unable to manufacture and distribute sufficient quantities to meet demand, our development and
commercialization efforts may be materially harmed.
We have no internal manufacturing or distribution capabilities. Instead, we rely on a combination of contract
manufacturers and our partners to manufacture API, finished drug product and finished goods for linaclotide, apraglutide, and
our other product candidates. For linaclotide, each of our partners is responsible for API, finished drug product and finished
goods manufacturing (including bottling and packaging) for its respective territories and distributing the finished goods to
wholesalers. We and/or our partners have commercial supply agreements with independent third parties to manufacture
linaclotide API. For apraglutide, we design and develop the manufacturing process together with CDMOs , and we rely on
these CDMOs and other third-party suppliers for the manufacture and supply, including filling and packaging of all the
components of the finished product for human use. Should we, or any of our partners or any third-party manufacturers we or
our partners engage, experience setbacks or challenges in our manufacturing efforts, our development and commercialization
efforts may be materially harmed.
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Each of our partners and the third-party manufacturers we or our partners engage, must comply with GMP and other
stringent regulatory requirements enforced by the U.S. FDA, EMA and other comparable foreign regulatory authorities in
other jurisdictions. These requirements include, among other things, quality control, quality assurance and the maintenance of
records and documentation, which occur in addition to our and our partners’ own quality assurance releases.
If we or a regulatory agency discovers previously unknown problems with a product, such as adverse events of
unanticipated severity or frequency, or problems with a facility where the product is manufactured, a regulatory agency may
impose restrictions on that product or the manufacturer, including withdrawal of the product from the market or suspension of
manufacturing. If we, our partners or the manufacturing facilities for our products fail to comply with applicable regulatory
requirements, a regulatory agency may take the following actions, among others:
●
issue warning letters or untitled letters;
●
impose civil or criminal penalties;
●
suspend or withdraw regulatory approval;
●
suspend any ongoing clinical trials;
●
refuse to approve pending applications or supplements to applications submitted by us or our partners;
●
impose restrictions on operations, including costly new manufacturing requirements; or
●
seize or detain products or require us to initiate a product recall.
Manufacturers of our products may be unable to comply with these GMP requirements and with other regulatory
requirements. We have little control over compliance with these regulations and standards by our partners and the third-party
manufacturers we or our partners engage.
In addition, we expect that apraglutide may be regulated by the U.S. FDA as a drug-device combination product. Our
third-party manufacturers may not be able to comply with GMP regulations applicable to drug-device combination products,
including applicable provisions of the U.S. FDA’s drug GMP regulations and device GMP requirements embodied in the
Quality System Regulation, or similar regulatory requirements outside the U.S.
Our partners and the third-party manufacturers we or our partners engage may experience problems with their
respective manufacturing and distribution operations and processes, including, for example, quality issues, such as product
specification and stability failures, procedural deviations, improper equipment installation or operation, utility failures,
contamination, natural disasters and public health epidemics. In addition, the raw materials necessary to make API for our
products and product candidates are acquired from a limited number of sources. Any delay or disruption in the availability of
raw materials or a change in raw material suppliers could result in production disruptions, delays or higher costs with
consequent adverse effects on us.
The manufacture of pharmaceutical products requires significant expertise and capital investment, including the
development of advanced manufacturing techniques and process controls. Manufacturers of pharmaceutical products often
encounter difficulties in commercial production. These problems include difficulties with production costs and yields, quality
control, including stability of the product and quality assurance testing, and shortages of qualified personnel, as well as
compliance with federal, state and foreign regulations and the challenges associated with complex supply chain management.
Even if our partners or the third-party manufacturers we or our partners engage do not experience problems and commercial
manufacturing is achieved, their maximum or available manufacturing capacities may be insufficient to meet commercial
demand. Finding alternative manufacturers or adding additional manufacturers requires a significant amount of time and
involves significant expense. New manufacturers would need to develop and implement the necessary production techniques
and processes, which along with their facilities, would need to be inspected and approved by the regulatory authorities in each
applicable territory.
If our partners or the third-party manufacturers we or our partners engage fail to adhere to applicable GMP or other
regulatory requirements, experience delays or disruptions in the availability of raw materials or experience
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manufacturing or distribution problems, we will suffer significant consequences, including product seizures or recalls, loss of
product approval, fines and sanctions, reputational damage, shipment delays, inventory shortages, inventory write-offs and
other product-related charges and increased manufacturing costs. If we experience any of these results, or if maximum or
available manufacturing capacities are insufficient to meet demand, our and our partners’ development or commercialization
efforts may be materially harmed.
If any of our linaclotide partners undergoes a change of control or in management, this may adversely affect our
collaborative relationship or the success of the commercialization of linaclotide in the U.S. or in the other countries where
it is approved, or the ability to achieve regulatory approval, launch and commercialize linaclotide in other territories.
We work jointly and collaboratively with partners on many aspects of the development, manufacturing and/or
commercialization of linaclotide. In doing so, we have established relationships with several key members of the management
teams of our linaclotide partners in functional areas such as development, quality, regulatory, drug safety and
pharmacovigilance, operations, marketing, sales, field operations and medical science. Further, the success of our
collaborations is highly dependent on the resources, efforts and skills of our partners and their key employees. As we and our
partners develop and commercialize linaclotide in the U.S. and the other countries where it is approved, and develop, launch
and commercialize linaclotide in other parts of the world, the drug’s success becomes more dependent on us maintaining
highly collaborative and well aligned partnerships. If any of our linaclotide partners undergoes a change of control or in
management, we would similarly need to reestablish many relationships and confirm alignment, including on our development
and commercialization strategy for linaclotide. Further, in connection with any change of control or change in management,
there is inherent uncertainty and disruption in operations, which could result in distraction, inefficiencies, and misalignment of
priorities. As a result, in the event of a change of control or in management at one of our linaclotide partners, we cannot be
sure that we will be able to successfully execute on our development and commercialization strategy for linaclotide in an
effective and efficient manner and without disruption or reduced performance. Finally, any change of control or in
management may result in a reprioritization of linaclotide within a partner’s portfolio, or such partner may fail to maintain the
financial or other resources necessary to continue supporting its portion of the development, manufacturing or
commercialization of linaclotide.
If any of our linaclotide partners undergoes a change of control and the acquirer either (i) is unable to perform such
partner’s obligations under its collaboration or license agreement with us or (ii) does not comply with the divestiture or certain
other provisions of the applicable agreement, we have the right to terminate the collaboration or license agreement and re-
acquire that partner’s rights with respect to linaclotide. If we elect to exercise these rights in such circumstances, we will need
to either establish the capability to develop, manufacture and commercialize linaclotide in that partnered territory on our own
or we will need to establish a relationship with a new partner. We have assembled a team that represents the functional areas
necessary to support the commercialization of LINZESS in the U.S. If AbbVie was subject to a change of control that allowed
us to further commercialize LINZESS in the U.S. on our own, and we chose to do so, we would need to enhance each of these
functional aspects, as well as develop others, to replace the capabilities that AbbVie was previously providing to the
collaboration. Any such transition might result in a period of reduced efficiency or performance by our operations and
commercialization teams, which could adversely affect our ability to commercialize LINZESS.
We do not have certain operational capabilities outside of the U.S. If AbbVie, Astellas or AstraZeneca was subject to
a change of control that allowed us to continue linaclotide’s development or commercialization anywhere outside of the U.S.
on our own, and we chose to do so rather than establishing a relationship with a new partner, we would need to build
operational capabilities in the relevant territory. In any of these situations, the development and commercialization of
linaclotide could be negatively impacted.
Risks Related to Regulatory, Legal and Compliance Matters
We face potential product liability exposure, and, if claims brought against us are successful, we could incur substantial
liabilities.
The use of our product candidates in clinical trials and the sale of our approved products, including the sale of
linaclotide, expose us to product liability claims. If we do not successfully defend ourselves against product liability
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claims, we could incur substantial liabilities. In addition, regardless of merit or eventual outcome, product liability claims may
result in:
●
decreased demand for approved products;
●
impairment of our business reputation;
●
withdrawal of clinical trial participants;
●
initiation of investigations by regulators;
●
litigation costs;
●
distraction of management’s attention from our primary business;
●
substantial monetary awards to patients or other claimants;
●
loss of revenues; and
●
the inability to commercialize our product candidates.
We currently have product liability insurance coverage for the commercial sale of our products and for the clinical
trials of our product candidates which is subject to industry-standard terms, conditions and exclusions. Our insurance coverage
may not be sufficient to reimburse us for expenses or losses associated with claims. Moreover, insurance coverage is
becoming increasingly expensive, and, in the future, we may not be able to maintain insurance coverage at a reasonable cost
or in sufficient amounts to protect us against losses. On occasion, large judgments have been awarded in lawsuits based on
drugs that had unanticipated side effects. A successful product liability claim or series of claims could cause our stock price to
decline and, if judgments exceed our insurance coverage, could decrease our cash and adversely affect our business.
We will incur significant liability if it is determined that we are promoting any “off-label” uses of our products.
Physicians are permitted to prescribe drug products and medical devices for uses that are not described in the
product’s labeling and that differ from those approved by the U.S. FDA or other applicable regulatory agencies. Such “off-
label” uses are common across medical specialties. Although the U.S. FDA and other regulatory agencies do not regulate a
physician’s choice of treatments, the U.S. FDA and other regulatory agencies do restrict manufacturer communications on off-
label use. Companies are not permitted to promote drugs or medical devices for off-label uses or to promote unapproved drugs
or medical devices. Accordingly, we do not permit promotion of any product that we develop, license, commercialize,
promote, co-promote or otherwise partner prior to approval or for any indication, population or use not described in or
consistent with such product’s labeling. The U.S. FDA and other regulatory and enforcement authorities actively enforce laws
and regulations prohibiting promotion of off-label uses and the promotion of products for which marketing approval has not
been obtained. A company that is found to have promoted off-label uses or have engaged in improper pre-approval promotion
will be subject to significant liability, including civil and administrative remedies as well as criminal sanctions. Even if it is
later determined that we were not in violation of these laws, we may be faced with negative publicity, incur significant
expenses defending our actions and have to divert significant management resources from other matters.
Notwithstanding the regulatory restrictions on off-label promotion, the U.S. FDA and other regulatory authorities
allow companies to engage in truthful, non-misleading, and non-promotional disease awareness and scientific exchange
concerning their products, investigational assets and therapeutic areas of interest. We intend to engage in disease awareness
and medical and scientific exchange and education activities and communicate with healthcare providers in compliance with
all applicable laws, regulatory guidance and industry best practices. Although we believe we have put in place a robust
compliance program, which is designed to ensure that all such activities are performed in a legal and compliant manner, we
cannot be certain that our program will address all areas of potential exposure and the risks in this area cannot be entirely
eliminated.
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If we fail to comply with healthcare and other regulations, we could face substantial penalties and our business, operations
and financial condition could be adversely affected.
The marketing of pharmaceutical and biopharmaceutical products and related arrangements with healthcare
providers, third-party payors, patients and other third parties in the healthcare industry are subject to a wide range of
healthcare laws and regulations within the U.S. and in foreign jurisdictions in which we operate. These laws and regulations
may constrain our business and/or financial arrangements. Within the U.S., federal laws and regulations include:
●
federal healthcare program anti-kickback laws, which prohibit, among other things, persons from offering,
soliciting, receiving or providing remuneration, directly or indirectly, to induce either the referral of an
individual for, or the purchasing or ordering of, a good or service for which payment may be made under federal
healthcare programs such as Medicare and Medicaid;
●
federal false claims laws which prohibit, among other things, individuals or entities from knowingly presenting,
or causing to be presented, information or claims for payment from Medicare, Medicaid, or other third-party
payors that are false or fraudulent, and which may apply to manufacturers for reasons including providing
coding and billing advice to customers or engaging in prohibited off-label promotional activities;
●
federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which prohibits executing a
scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters and
which also imposes certain requirements relating to the privacy, security and transmission of individually
identifiable health information on certain types of entities, which include many healthcare providers with whom
we interact and health plans with which we may interact;
●
the Federal Food, Drug, and Cosmetic Act, which among other things, strictly regulates drug product and
medical device marketing, prohibits manufacturers from marketing such products prior to approval or for off-
label use and regulates the distribution of samples;
●
the 21st Century Cures Act, which amends Section 114 of the Food and Drug Administration Modernization Act
of 1997 to define healthcare economic information and the circumstances under which healthcare economic
information may be disseminated;
●
federal laws, including the Medicaid Drug Rebate Program, that require pharmaceutical manufacturers to report
certain calculated product prices to the government or provide certain discounts or rebates to government
authorities or private entities, often as a condition of reimbursement under government healthcare programs; and
●
the so-called “federal sunshine” law, which requires pharmaceutical and medical device companies to monitor
and report certain financial interactions with physicians, certain non-physician practitioners and teaching
hospitals to the federal government for re-disclosure to the public.
There are also state law equivalents of certain of the above federal laws, many of which differ from each other in
significant ways and often are not preempted by federal laws, thus complicating compliance efforts, which laws include anti-
kickback and false claims laws, which may apply to items or services reimbursed by any third-party payor, including
commercial insurers, state transparency laws, state laws limiting interactions between pharmaceutical manufacturers and
members of the healthcare industry, and state laws governing the privacy and security of health information in certain
circumstances.
Other laws and regulations have also been enacted by various states to regulate the sales and marketing practices of
pharmaceutical or biopharmaceutical manufacturers. The laws and regulations generally limit financial interactions between
manufacturers and health care providers; require manufacturers to comply with the pharmaceutical industry’s voluntary
compliance guidelines and the relevant compliance guidance promulgated by the U.S. federal government; and/or require
disclosure to the government and/or public of financial interactions (so-called “sunshine laws”). State laws may also require
disclosure of pharmaceutical pricing information and marketing expenditures. Certain state and local laws require the
registration of pharmaceutical sales representatives. Additionally, some
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individual states have begun establishing Prescription Drug Affordability Boards (or similar entities) to review high-cost drugs
and, in some cases, set upper payment limits. Many of these laws and regulations contain ambiguous requirements or require
administrative guidance for implementation.
Outside the U.S., our activities may be subject to healthcare laws. For example, the provision of benefits or
advantages to physicians to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order, or
use of medicinal products is prohibited in the E.U. The provision of benefits or advantages to physicians is also governed by
the national anti-bribery laws of E.U. Member States, and by Bribery Act 2010 in the United Kingdom. Infringement of these
laws could result in substantial fines and imprisonment.
Payments made to physicians in certain E.U. Member States must be publicly disclosed, and in the United Kingdom
a public consultation on the introduction of equivalent transparency requirements is currently underway. Moreover,
agreements with physicians often must be the subject of prior notification and approval by the physician’s employer, his or her
competent professional organization, and/or the regulatory authorities of the individual E.U. Member States and the United
Kingdom. These requirements are provided in the national laws, self-regulatory industry codes, or professional codes of
conduct applicable in the E.U. Member States and the United Kingdom. Failure to comply with these requirements could
result in reputational risk, public reprimands, administrative penalties, fines, or imprisonment.
We also are subject to the FCPA which prohibits corporations and individuals from paying, offering to pay, or
authorizing the payment of anything of value to any foreign government official, government staff member, political party, or
political candidate in an attempt to obtain or retain business or to otherwise influence a person working in an official capacity,
related to any ex-U.S. activities, as well as other similar anti-bribery laws in any other country in which we may do business.
It is possible that governmental authorities will conclude that our business practices, or the business practices of third
parties with whom we collaborate, may not comply with current or future statutes, regulations or case law involving
applicable fraud and abuse or other healthcare laws and regulations. If our operations, or those of third party partners, are
found to be in violation of any of these laws or any other governmental regulations, we may be subject to lawsuits, significant
civil, criminal and administrative penalties, damages, fines, exclusion from government funded healthcare programs, such as
Medicare and Medicaid, and the curtailment or restructuring of our operations.
We are subject to stringent and changing U.S. and foreign laws, regulations, rules, contractual obligations, policies and
other obligations related to data privacy and security. Our actual or perceived failure to comply with such obligations could
lead to regulatory investigations or actions; litigation; fines and penalties; disruptions of our business operations;
reputational harm; loss of revenue or profits; disruptions of our operating results and business; and other adverse business
consequences.
We may be subject to privacy and security laws in the various jurisdictions, both inside and outside the U.S., in which
we operate and/or obtain or store personally identifiable information, such as the E.U. GDPR, the United Kingdom’s GDPR
and the Swiss Federal Act on Data Protection, or FADP. The legislative and regulatory landscape for privacy and data
protection continues to evolve, and there has been an increasing focus on privacy and data protection issues with the potential
to affect our business. For example, the GDPR, which took effect in May 2018, applies to the processing of personal data in
the EEA. The GDPR increases obligations with respect to clinical trials and non-clinical studies conducted in the EEA, by
certain companies that process data in relation to (i) offering goods or services to, or (ii) monitoring the behavior of,
individuals located in the EEA. As such, we are subject to the GDPR for data processing associated, for example, with
conducting clinical trials in the EEA or entering into research collaborations in the EEA. The GDPR imposes stringent
obligations for processing of personal data, such as setting high standards for consent, requiring the provision of detailed
processing notices, facilitating the exercise of data subject rights and requiring reporting certain data breaches to regulators
and affected individuals, as well as establishing standards for how we document our relationships with third parties that
process GDPR-covered personal data on our behalf. The FADP also applies to the collection and processing of personal data
by companies located in Switzerland, or in certain circumstances, by companies located outside of Switzerland. The FADP has
been revised and adopted by the Swiss Parliament and took effect on September 1, 2023. The revisions to the FADP may
result in increased costs of compliance, risks of noncompliance and penalties for noncompliance.
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The GDPR, United Kingdom’s GDPR and FADP also increase the scrutiny applied to transfers of personal data from
the EEA, UK, and Switzerland, respectively (including from clinical trial sites in the EEA) to countries that are considered by
the European Commission, United Kingdom or Switzerland, respectively, to lack an adequate level of data protection, such as
the U.S. In July 2020 the Court of Justice of the E.U. (CJEU) invalidated the E.U.-U.S. Privacy Shield Framework, under
which personal data could be transferred from the EEA to U.S. entities that had self-certified under the Privacy Shield scheme.
The framework has been replaced by the E.U.-U.S. Data Privacy Framework for which the European Commission adopted an
adequacy decision in July 2023. While we do not currently rely upon this framework, we expect there to be legal challenges to
this framework in the future, which could draw into question the legitimacy of other cross-border transfer mechanism,
including the standard contractual clauses on which we rely to transfer personal data from the EEA to the U.S. and other
jurisdictions. As supervisory authorities issue further guidance on personal data export mechanisms or where the standard
contractual clauses cannot be used, we could incur additional compliance costs, complaints, and/or regulatory investigations
and, if we are unable to otherwise transfer personal data among jurisdictions in which we operate, our services and
geographical location or segregation of our relevant systems and operations could be affected.
In addition, in the U.S., we are subject to the CCPA, as amended by the CPRA, which became effective on January 1,
2023 (the CPRA, together with CCPA, the California Privacy Law). The California Privacy Law gives California consumers
(defined to include all California residents) certain rights regarding personal information collected about them; the California
Privacy Law also imposes certain obligations and limitations on companies regarding the collection, use, selling or sharing (as
defined in the California Privacy Law) of personal information collected from or about California consumers. Other states
have passed comprehensive privacy laws specifically regulating health information that may affect our business. For example,
Washington state recently passed the My Health My Data Act to which we are subject, which regulates the collection and
sharing of health information, and provides a right of action for violation of the statute.
The compliance obligations imposed by the GDPR, United Kingdom’s GDPR, FADP, the California Privacy Law,
Washington’s My Health My Data Act, and other applicable privacy laws, have required us to revise our operations. Breaches
of applicable data protection requirements may result in substantial fines and other regulatory penalties, as well as confer a
private right of action on data subjects or consumers and their representatives for breaches of certain data protection
requirements. We expect to be subject to additional privacy laws at both the U.S. state level and abroad as many jurisdictions
either recently have data privacy legislation or are considering enacting such legislation to which we may become subject.
Achieving and sustaining compliance with applicable international, federal and state privacy, security, fraud and reporting
laws may prove time-consuming and costly.
If our operations, or the operations of third parties upon which we rely, are found to be in violation of any of the laws
described above or any other laws, rules or regulations that apply to us, we will be subject to penalties, including civil and
criminal penalties, damages, fines and the curtailment or restructuring of our operations. For example, under the GDPR and
the United Kingdom’s GDPR, penalties for noncompliance could be up to 20 million Euros or 4% of our total worldwide
annual revenue of the preceding financial year, whichever is greater. Any penalties, damages, fines, curtailment or
restructuring of our operations could adversely affect our ability to operate our business and our financial results. Although
compliance programs can mitigate the risk of investigation and prosecution for violations of these laws, rules or regulations,
we cannot be certain that our program will address all areas of potential exposure and the risks in this area cannot be entirely
eliminated, particularly because the requirements and government interpretations of the requirements in this space are
constantly evolving. Any action against us for violation of these laws, rules or regulations, even if we successfully defend
against it, could cause us to incur significant legal expenses and divert our management’s attention from the operation of our
business, as well as damage our business or reputation.
The VectivBio Acquisition increases our exposure to doing business in foreign jurisdictions.
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Following the VectivBio Acquisition, we retained VectivBio’s legacy headquarters in Basel, Switzerland and, as a
result, we now have employees and operations in foreign jurisdictions. Operating in foreign jurisdictions exposes us to
additional risks such as fluctuations in currency exchange rates; compliance with different legal and regulatory environments;
foreign regulatory regimes applicable to clinical trials and obtaining approvals for product candidates; compliance with
applicable data privacy laws and regimes such as the E.U. GDPR, the United Kingdom’s GDPR and the Swiss FADP; risk
relating to the political and economic status of foreign governments; differences in the manner in which different cultures do
business; difficulties in staffing and managing foreign operations; differences in financial reporting; and operating difficulties;
among other factors. The realization of any of these risks, if severe enough, could have an adverse effect on our consolidated
financial position, results of operations and cash flows.
Risks Related to Intellectual Property
Limitations on our ability to obtain patent protection and/or the patent rights relating to our products and our product
candidates may limit our ability to prevent third parties from competing against us.
Our success depends on our ability to obtain and maintain sufficient patent protection for our products and product
candidates, preserve our trade secrets, prevent third parties from infringing upon our proprietary rights and operate without
infringing upon the proprietary rights of others.
The strength of patents in the pharmaceutical industry involves complex legal and scientific questions and can be
uncertain. Patent applications in the U.S. and most other countries are confidential for a period of time until they are
published, and publication of discoveries in scientific or patent literature typically lags actual discoveries by several months or
more. As a result, we cannot be certain that we were the first to conceive inventions covered by our patents and pending patent
applications or that we were the first to file patent applications for such inventions. In addition, we cannot be certain that our
patent applications will be granted, that any issued patents will adequately protect our intellectual property, or that such
patents will not be challenged, narrowed, invalidated or circumvented.
We have several issued patents in the U.S. related to LINZESS, including a LINZESS composition of matter and
methods of use patent (U.S. Patent 7,304,036) expiring in 2026. Additional U.S. patents related to LINZESS include multiple
patents relating to our commercial, room temperature stable formulations of the 72 mcg, 145 mcg and 290 mcg doses of
linaclotide and methods of using these formulations, the latest of which expires in the early 2030s, as well as other patents and
patent applications covering formulations of linaclotide, and molecules related to linaclotide.
In addition, we have exclusive rights to apraglutide including issued composition of matter and method of use patents
in the U.S. in lead indications. We aim to maintain a strong and broad estate of patents in the U.S. and other geographic areas.
To this end, we have exclusively licensed 57 patents and 3 pending patent applications in the U.S., E.U., Japan, China and
other jurisdictions protecting apraglutide. We also own one U.S. granted patent and one granted Japanese patent as well as
approximately 38 pending patent applications worldwide that cover apraglutide, including ultrapure compositions, methods of
manufacture and methods of use in various diseases.
Although none of these issued patents currently is subject to a patent reexamination or review, we cannot guarantee
that they will not be subject to reexamination or review by the USPTO in the future. We believe in the strength of our
LINZESS and apraglutide patent portfolio and that we have sufficient freedom to operate; however, if any of our present or
future patents is challenged, narrowed, invalidated or circumvented, or our pending patent applications are not granted, our
ability to prevent third parties from competing with LINZESS or apraglutide could be limited and our business and financial
results may be materially harmed.
Furthermore, the America Invents Act, which was signed into law in 2011, has made several major changes in the
U.S. patent statutes. These changes permit third parties to challenge our patents more easily and create uncertainty with
respect to the interpretation and practice of U.S. patent law. Moreover, the U.S. Supreme Court has ruled on several patent
cases that narrow the scope of patent protection available and weakening the rights of patent owners in certain circumstances.
Depending on the impact of these decisions and other actions by the U.S. Congress, the federal courts, the USPTO, and their
foreign counterparts, the laws and regulations governing patents may change, or their interpretation or implementation may
change, in unpredictable ways that could impact, potentially adversely, our ability to obtain new patents or to enforce and
defend patents that we have already obtained or that we might obtain in the
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future. For example, such changes may increase the costs and complexity associated with obtaining, enforcing or defending
our patents, including in ANDA litigation.
We also rely upon unpatented trade secrets, unpatented know-how and continuing technological innovation to
develop and maintain our competitive position, which we seek to protect, in part, by confidentiality agreements with our
employees and our partners and consultants. We also have agreements with our employees and selected consultants that
obligate them to assign their inventions to us. It is possible, however, that technology relevant to our business will be
independently developed by a person that is not a party to such an agreement. Furthermore, if the employees and consultants
that are parties to these agreements breach or violate the terms of these agreements, we may not have adequate remedies, and
we could lose our trade secrets through such breaches or violations. Additionally, our trade secrets could otherwise become
known or be independently discovered by our competitors.
In addition, the laws of certain foreign countries do not protect proprietary rights to the same extent or in the same
manner as the U.S., and, therefore, we or our partners may encounter problems in protecting and defending our intellectual
property in certain foreign jurisdictions.
If we are sued for infringing intellectual property rights of third parties, it will be costly and time consuming, and an
unfavorable outcome in such litigation could have a material adverse effect on our business.
Our commercial success depends on our ability, and the ability of our partners, to develop, manufacture, market and
sell our products and use our proprietary technologies without infringing the proprietary rights of third parties.
Numerous U.S. and foreign issued patents and pending patent applications, which are owned by third parties, exist in the
fields in which we and our partners are developing products. As the biotechnology and pharmaceutical industry expands and
more patents are issued, the risk increases that our potential products may give rise to claims of infringement of the patent
rights of others. There may be issued patents of third parties of which we are currently unaware that may be infringed by
LINZESS, apraglutide, or our product candidates. Because patent applications can take many years to issue, there may be
currently pending applications which may later result in issued patents that LINZESS, apraglutide, or our product candidates
may infringe.
We may be exposed to, or threatened with, litigation by third parties alleging that LINZESS, apraglutide, or our
product candidates infringe their intellectual property rights. If LINZESS, apraglutide, or one of our product candidates is
found to infringe the intellectual property rights of a third party, we or our partners could be enjoined by a court and required
to pay damages and could be unable to develop or commercialize LINZESS, apraglutide, or the applicable product candidate
unless we obtain a license to the intellectual property rights. A license may not be available to us on acceptable terms, if at all.
In addition, during litigation, the counterparty could obtain a preliminary injunction or other equitable relief which could
prohibit us from making, using or selling our products, pending a trial on the merits, which may not occur for several years.
There is a substantial amount of litigation involving patent and other intellectual property rights in the biotechnology
and pharmaceutical industries generally. If a third party claims that we or our partners infringe its intellectual property rights,
we may face a number of issues, including, but not limited to:
●
infringement and other intellectual property claims which, regardless of merit, may be expensive and time-
consuming to litigate and may divert our management’s attention from our core business;
●
substantial damages for infringement, which we may have to pay if a court decides that the product at issue
infringes on or violates the third party’s rights, and, if the court finds that the infringement was willful, we could
be ordered to pay treble damages and the patent owner’s attorneys’ fees;
●
a court prohibiting us from selling our product unless the third party licenses its rights to us, which it is not
required to do;
●
if a license is available from a third party, we may have to pay substantial royalties, fees or grant cross- licenses
to our intellectual property rights; and
●
redesigning our products so they do not infringe, which may not be possible or may require substantial monetary
expenditures and time.
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If we fail to comply with our obligations or have disagreements over contract interpretation in agreements under which we
license intellectual property and other rights from third parties or otherwise experience disruptions to our business
relationship with our licensor, the scope of our intellectual property or technology rights could be narrowed and we could
lose license rights that are important to our business.
Licensing of intellectual property is of critical importance to our business and involves complex legal, business, and
scientific issues. Disputes may arise regarding intellectual property subject to a licensing agreement, including but not limited
to:
●
the scope of rights granted under the license agreement and other interpretation-related issues;
●
the extent to which our technology and processes infringe intellectual property of the licensor that is not subject
to the licensing agreement;
●
the sublicensing of patent and other rights;
●
our diligence obligations under the license agreement and what activities satisfy those diligence obligations;
●
the ownership of inventions and know-how resulting from the joint creation or use of intellectual property by
our licensors, our collaborators and us;
●
the priority of invention of patented technology; and
●
the fulfilment of our obligations under the license.
In addition, certain provisions in such agreements may be susceptible to multiple interpretations. The resolution of
any contract interpretation disagreement that may arise could narrow what we believe to be the scope of our rights to the
relevant intellectual property or technology, or increase what we believe to be our financial or other obligations under the
relevant agreement, either of which could harm our business, financial condition, results of operations and prospects. If our
licenses or material relationships or any in-licenses upon which our licenses are based are terminated or breached, we may:
●
lose our rights to develop and market product candidates;
●
lose patent protection for product candidates;
●
experience significant delays in the development or commercialization of product candidates;
●
not be able to obtain any other licenses on acceptable terms, if at all; or
●
incur liability for damages.
We are currently a party to and may in the future be party to license agreements. Apraglutide is among the assets that
are subject to licensing agreements with third parties. For example, we are a party to an amended and restated intellectual
property license agreement with Ferring pursuant to which we have exclusive rights to apraglutide including an issued
composition of matter and method of use patent in the U.S. in lead indications, or the Ferring Agreement. The Ferring
Agreement imposes, and other current or future license agreements may impose, various diligence, milestone payment,
royalty, and other obligations on us. These milestone, royalty, and other payments associated with the license, will make it less
profitable for us to develop apraglutide or other product candidates that are the subject of current or future licenses. If we fail
to comply with our obligations under the Ferring Agreement, or we are subject to a bankruptcy, we may be required to make
certain payments to Ferring, we may lose the exclusivity of our license, or Ferring may have the right to terminate the license.
If the Ferring Agreement is terminated, we could lose intellectual property rights that are important to our business, be liable
for damages to the licensor or be prevented from developing and
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commercializing our apraglutide. Termination of the agreement or reduction or elimination of our rights under the agreement
may also result in us being required to negotiate a new or reinstated agreement with less favorable terms, and it is possible that
we may be unable to obtain any such additional license at a reasonable cost or on reasonable terms and will be unable to
develop and commercialize apraglutide. These or similar risks may apply to other license agreements, including future license
agreements. If disputes over intellectual property and other rights that we have licensed prevent or impair our ability to
maintain our current licensing arrangements on acceptable terms, we may be unable to successfully develop and
commercialize apraglutide.
In some cases, patent prosecution of our licensed technology is controlled solely by the licensor. If our licensor fails
to obtain or maintain a patent or other protection for the proprietary intellectual property we license from them, we could lose
our rights to the intellectual property or our exclusivity with respect to those rights, and our competitors could market
competing products using the intellectual property. In certain cases, we control the prosecution of patents resulting from
licensed technology. In the event we breach any of our obligations related to such prosecution, we may incur significant
liability to our licensing partners.
We may be unable to maintain the benefits associated with orphan drug designation, including market exclusivity, which
may harm our business.
In the U.S., orphan drug designation entitles a party to financial incentives such as opportunities for grant funding
towards clinical trial costs, tax advantages, and user-fee waivers. In addition, if a product receives the first U.S. FDA approval
for the indication for which it has orphan designation, the product is entitled to orphan drug exclusivity, which means the U.S.
FDA may not approve any other application to market the same drug for the same indication for a period of seven years,
except in limited circumstances, such as a showing of clinical superiority over the product with orphan exclusivity or where
the manufacturer is unable to assure sufficient product quantity. In the E.U., orphan drug designation entitles a company to
financial incentives such as reduction of fees or fee waivers and ten years of data and market exclusivity for the approved
therapeutic indication following marketing authorization of a medicinal product, including biological medicinal products. This
period may be reduced to six years if, at the end of the fifth year, the medicinal product no longer fulfills the orphan
designation criteria, including where it is shown that the product is sufficiently profitable not to justify maintenance of market
exclusivity.
Because the extent and scope of patent protection for our products may in some cases be limited, orphan drug
designation is especially important for our product candidates for which orphan drug designation may be available. For
eligible drugs, we plan to rely on the exclusivity period under the Orphan Drug Act to maintain a competitive position. If we
do not obtain orphan drug exclusivity for our drug product candidates that does not have a broad patent protection, our
competitors may then sell the same drug to treat the same condition sooner than if we had obtained orphan drug exclusivity
and our revenue will be reduced.
Even though we have orphan drug designation for apraglutide in the U.S. and in the E.U., we may not be the first to
obtain marketing approval for any particular orphan indication due to the uncertainties associated with developing
pharmaceutical products. Based on available preclinical and clinical data, both the U.S. FDA and the EMA have granted
apraglutide orphan drug designation for the treatment of SBS. Orphan drug applicability will be reassessed by health
authorities upon completion of clinical studies and submission of our marketing application. In the E.U., the orphan
designation for apraglutide may not be maintained at the time of grant of the marketing authorization if the EMA and COMP
do not consider that there is sufficient confirmatory evidence to support that the orphan designation criteria continue to be met.
Even if we obtain orphan drug exclusivity for a product, that exclusivity may not effectively protect the product from
competition because different drugs with different active moieties can be approved for the same condition. Even after an
orphan drug is approved, the U.S. FDA or EMA can subsequently approve the same drug with the same active moiety for the
same condition if the U.S. FDA or EMA concludes that the later drug is safer, more effective, or makes a major contribution to
patient care. Orphan drug designation neither shortens the development time or regulatory review time of a drug nor gives the
drug any advantage in the regulatory review or approval process.
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We have received notices of Paragraph IV certifications related to LINZESS in conjunction with ANDAs filed by generic
drug manufacturers, and we may receive additional notices from others in the future. We have, and may continue to,
become involved in legal proceedings to protect or enforce intellectual property rights relating to our products and our
product candidates, which could be expensive and time consuming, and unfavorable outcomes in such proceedings could
have a material adverse effect on our business.
Competitors may infringe the patents relating to our products and our product candidates or may assert that such
patents are invalid. To counter ongoing or potential infringement or unauthorized use, we may be required to file infringement
claims, which can be expensive and time-consuming. Litigation with generic manufacturers has become increasingly common
in the biotechnology and pharmaceutical industries. In addition, in an infringement or invalidity proceeding, a court or patent
administrative body may determine that a patent of ours is not valid or is unenforceable, or may refuse to stop the other party
from using the technology at issue on the grounds that our patents do not cover the technology in question.
Generic drug manufacturers were first able to file ANDAs for generic versions of LINZESS in August 2016. When
filing an ANDA for one of our products, a generic drug manufacturer may choose to challenge one or more of the patents that
cover such product and seek to commercialize generic versions of one or more LINZESS doses. As such, we have brought,
and may bring in the future, legal proceedings against generic drug manufacturers.
We and AbbVie have received Paragraph IV certification notice letters regarding ANDAs submitted to the U.S. FDA
by generic drug manufacturers requesting approval to engage in commercial manufacture, use, sale and offer for sale of
linaclotide capsules (72 mcg, 145 mcg and 290 mcg), proposed generic versions of our U.S. FDA-approved drug LINZESS.
We filed patent infringement lawsuits against five companies making such ANDA filings and subsequently entered into
settlement agreements with each of these filers. Frequently, innovators receive multiple ANDA filings. Consequently, we may
receive additional notice letters regarding ANDAs submitted to the U.S. FDA (and we may receive amendments to those
notice letters), but we may not become aware of these filings for several months after any such submission due to procedures
specified under applicable U.S. FDA regulations.
After evaluation, we have in the past filed, and may, in the future, file patent infringement lawsuits or take other
action against companies making ANDA filings. If a patent infringement suit has been filed within 45 days of receipt of a
notice letter, the U.S. FDA is not permitted to approve any ANDA that is the subject of such lawsuit for 30 months from the
date of the NDA holder’s and patent owner’s receipt of the ANDA filer’s notice letter, or until a court decides that the relevant
patents are invalid, unenforceable and/or not infringed. Additionally, the validity of the patents relating to our products and
our product candidates may be challenged by third parties pursuant to administrative procedures introduced by the America
Invents Act, specifically inter partes review, or IPR, and/or post grant review, or PGR, before the USPTO. Generic drug
manufacturers may challenge our patents through IPRs or PGRs instead of or in addition to ANDA legal proceedings.
Patent litigation (including any lawsuits that we file against generic drug manufacturers in connection with the
receipt of a notice letter), IPRs and PGRs involve complex legal and factual questions and we may need to devote significant
resources to such legal proceedings. We can provide no assurance concerning the duration or the outcome of any such patent-
related lawsuits or administrative proceedings, including any settlements or other resolutions thereof which could, in addition
to other risks, result in a shortening of exclusivity periods. An adverse result in any litigation or defense proceedings could put
one or more of the patents relating to our products and our product candidates at risk of being invalidated or interpreted
narrowly, or could otherwise result in a loss of patent protection for the product or product candidate at issue, and could put
our patent applications at risk of not issuing, which would materially harm our business. Upon any loss of patent protection
for one of our products, or upon an “at-risk” launch (despite pending patent infringement litigation, before any court decision
or while an appeal of a lower court decision is pending) by a manufacturer of a generic version of one of our patented
products, our revenues for that product could be significantly reduced in a short period of time, which would materially and
adversely affect our business.
Interference or derivation proceedings brought by the USPTO may be necessary to determine the priority of
inventions with respect to the patents relating to our products and our product candidates and patent applications or those of
our partners. An unfavorable outcome could require us to cease using the technology or to attempt to license rights to it from
the prevailing party. Our business could be harmed if a prevailing party does not offer us a license on terms that are acceptable
to us. Litigation or interference proceedings may fail and, even if successful, may result in substantial costs and distraction of
our management and other employees. In addition, we may not be able to prevent, alone or with
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our partners, misappropriation of our proprietary rights, particularly in countries where the laws may not protect those rights
as fully as in the U.S.
Furthermore, because of the substantial amount of discovery required in connection with intellectual property
litigation, as well as the potential for public announcements of the results of hearings, motions or other interim proceeding or
developments, there is a risk that some of our confidential information could be compromised by disclosure during this type of
litigation.
Risks Related to Our Finances and Capital Requirements
We incurred significant losses from our inception in 1998 through the year ended December 31, 2018, and we may incur
losses in future periods.
In recent years, we have focused primarily on developing, manufacturing and commercializing linaclotide, as well as
developing our other product candidates. For example, in June 2023, we acquired VectivBio and added apraglutide, a next
generation long-acting GLP-2 analog, in development for the treatment of patients with SBS who are dependent on PS, to our
pipeline. We have financed our business to date primarily through the issuance of equity, our collaboration and license
arrangements, and debt issuances, including our $200.0 million aggregate principal amount of Convertible Senior Notes,
bearing an interest of 1.50% and due in 2026, or the Convertible Senior Notes, and our $550.0 million secured revolving
credit facility, or the Revolving Credit Facility. We currently derive a significant portion of our revenue from our LINZESS
collaboration with AbbVie for the U.S. We believe that the revenues from the LINZESS collaboration will continue to
constitute a significant portion of our total revenue for the foreseeable future. Such revenue is highly dependent on LINZESS
demand and other factors such as fluctuations in retail chains’ and wholesalers’ buying patterns and inventory levels, pricing
and reimbursement. Our collaborative arrangements revenue outside of the U.S. has and 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
current and future strategic partnerships outside of the U.S.
For the year ended December 31, 2023, we incurred a net loss in connection with the VectivBio Acquisition. Prior to
the year ended December 31, 2019, we incurred net losses in each year since our inception in 1998. As of December 31, 2024,
we had an accumulated deficit of approximately $1.7 billion. We cannot be certain that sales of our products, and the revenue
from our other commercial activities, will not fall short of our projections or be delayed. Further, we expect to continue to
incur substantial expenses in connection with our efforts to commercialize linaclotide and, if approved, apraglutide, research
and develop our product candidates, and access externally developed products or product candidates. Because of the numerous
risks and uncertainties associated with developing and commercializing pharmaceutical products, as well as those related to
our expectations for our products and our other activities, we are unable to predict the extent of any future losses. Failure to
achieve sustainable net income and maintain positive cash flows would have an adverse effect on stockholders’ equity and
working capital.
We may need additional funding and may be unable to raise capital when needed, which could cause us to delay, reduce or
eliminate our corporate or product development or commercialization efforts.
We have previously raised funds to finance our operations through capital raising activities, including the sale of
shares of our Class A Common Stock in public offerings and convertible and other debt issuances. However, marketing and
selling gastrointestinal drugs, purchasing commercial quantities of pharmaceutical products, developing product candidates,
conducting clinical trials and accessing externally developed products or product candidates are expensive and uncertain.
Circumstances, our strategic imperatives, or opportunities to create or acquire new programs, as well as maturities,
redemptions or repurchases of our outstanding debt securities, could require us to, or we may choose to, seek to raise
additional funds. The amount and timing of our future funding requirements will depend on many factors, including, but not
limited to:
●
the level of underlying demand and price we are able to charge for our products in the countries in which they
are approved;
●
the costs associated with commercializing our products in the U.S.;
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●
the costs of establishing, maintaining and/or expanding sales, marketing, distribution, and market access
capabilities for our products;
●
the regulatory approval of linaclotide within new indications, populations and formulations, as well as the
associated development and commercial milestones and royalties;
●
the regulatory approvals of apraglutide;
●
the rate of progress, the cost of our clinical trials and the other costs associated with our development programs,
including our clinical trial of apraglutide in adult patients with SBS-IF, post-approval nonclinical and clinical
studies of linaclotide in pediatrics and our investment to enhance the clinical profile of LINZESS within IBS-C
and CIC, as well as to study linaclotide in additional indications, populations and formulations to assess its
potential to treat various conditions;
●
the costs and timing of in-licensing additional products or product candidates or acquiring other complementary
companies or assets;
●
the status, terms and timing of any collaboration, licensing, co-commercialization or other arrangements;
●
whether the holders of our Convertible Senior Notes hold the notes to maturity without conversion into our
Class A Common Stock or cash and whether we are required to repurchase any of our Convertible Senior Notes
prior to maturity upon a fundamental change, as defined in each of the indentures governing the Convertible
Senior Notes; and
●
whether we seek to redeem, repurchase or retire all or part of our outstanding debt through cash purchases and/or
exchanges, in open market purchases, privately negotiated transactions, by tender offer or otherwise.
Additional funding may not be available on acceptable terms or at all. If adequate funds are not available, we may be
required to delay or reduce the scope of our commercialization efforts, delay, reduce or eliminate one or more of our
development programs or delay or abandon potential strategic opportunities.
Our ability to pay principal of and interest on our outstanding debt will depend in part on the receipt of payments from
AbbVie under our collaboration agreement for North America.
Semi-annual payments on our Convertible Senior Notes began in December 2019. In addition, in 2023, we entered
into the Revolving Credit Facility. As of December 31, 2024, the outstanding principal balance on the Revolving Credit
Facility was $385.0 million. We expect that for the next few years, at a minimum, the net quarterly payments from AbbVie
will be a significant source of cash flows from operations. If the cash flows derived from the net quarterly payments that we
receive from AbbVie under the collaboration agreement for North America are insufficient on any particular payment date to
fund the interest payment on our outstanding indebtedness, at a minimum, we will be obligated to pay the amounts of such
shortfall out of our general funds. The determination of whether AbbVie will be obligated to make a net quarterly payment to
us in respect of a particular quarterly period is a function of the revenue generated by LINZESS in the U.S. as well as the
development, manufacturing and commercialization expenses incurred by each of us and AbbVie under the collaboration
agreement for North America. Accordingly, since we cannot guarantee that our company will maintain net income or positive
cash flows, we cannot provide assurances for any particular quarterly period that (i) we will have the available funds to fund
the interest payment on our outstanding indebtedness, at a minimum, in the event that there is a deficiency in the net quarterly
payment received from AbbVie, (ii) there will be a net quarterly payment from AbbVie at all or (iii) we will not also be
required to make a true-up payment to AbbVie under the collaboration agreement for North America.
Our indebtedness could adversely affect our financial condition or restrict our future operations.
As of December 31, 2024, we had total indebtedness of $585.0 million and available cash and cash equivalents of
$88.6 million.
We incurred significant new indebtedness in connection with the VectivBio Acquisition. In May 2023, we entered
into the Revolving Credit Facility, which includes a $10.0 million letter of credit subfacility. In June 2023, we
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borrowed $400.0 million to fund a portion of the consideration paid to purchase VectivBio’s outstanding ordinary shares in
connection with the VectivBio Acquisition.
The agreement governing the Revolving Credit Facility, or the Revolving Credit Agreement, as amended in
September 2024, contains certain covenants applicable to us and certain of our subsidiaries that may, under certain
circumstances, impose significant operating and financial restrictions on us, including, without limitation, limitations on
additional indebtedness, liens, various fundamental changes, dividends and distributions, investments (including acquisitions),
transactions with affiliates, asset sales, prepayment of junior financing, changes in business and other limitations customary in
senior secured credit facilities. The Revolving Credit Agreement also includes cross-default features providing that defaults
under certain other indebtedness would result in a default under the Revolving Credit Agreement. In addition, the Revolving
Credit Agreement requires us to maintain a maximum consolidated secured net leverage ratio of 3.50 to 1.00 until the end of
the final quarter of 2025, or the Initial Period, (ii) 3.25 to 1.00 until the end of the first quarter of 2026, or the Interim Period,
and (iii) 3.00 to 1.00 thereafter, and a minimum interest coverage ratio of 3.00 to 1.00, in each case at the end of each fiscal
quarter. The Revolving Credit Agreement allows us to elect to increase the permitted maximum consolidated secured net
leverage ratio to (i) 4.00 to 1.00 during the Initial Period, (ii) 3.75 to 1.00 during the Interim Period, and (iii) 3.50 to 1.00
thereafter, in each case for up to for four fiscal quarters in the event it consummates an acquisition for consideration in excess
of $50.0 million, subject to certain limitations on how often this election can be made. Additionally, the lenders under the
Revolving Credit Agreement will be permitted to accelerate all outstanding borrowings and other obligations, terminate
outstanding commitments and exercise other specified remedies upon the occurrence of customary events of default.
In addition, while the indenture governing our Convertible Senior Notes does not include covenants restricting the
operation of our business except in certain limited circumstances, in the event of a default under the Convertible Senior Notes,
the noteholders or the trustee under the indenture governing the Convertible Senior Notes may accelerate our payment
obligations under the Convertible Senior Notes, which could have a material adverse effect on our business, financial
condition and results of operations. We are also required to offer to repurchase the Convertible Senior Notes upon the
occurrence of a fundamental change, which could include, among other things, any acquisition of our company (other than an
acquisition in which at least 90% of the consideration is Class A Common Stock listed on The Nasdaq Global Select Market or
The New York Stock Exchange), subject to the terms of the indenture governing the Convertible Senior Notes. The repurchase
price must be paid in cash, and this obligation may have the effect of discouraging, delaying or preventing an acquisition of
our company that would otherwise be beneficial to our security holders.
The indenture governing our Convertible Senior Notes also includes cross-default features providing that certain
failures to pay for outstanding indebtedness would result in a default under the indenture governing our Convertible Senior
Notes. In the event of such default, the trustee or noteholders could elect to declare all amounts outstanding to be immediately
due and payable under the indenture, which could have a material adverse effect on our business, financial condition and
results of operations.
To the extent we become subject to such covenants, our ability to comply with such covenants in future periods will
depend on our ongoing financial and operating performance, which in turn will be subject to economic conditions and to
financial, market and competitive factors, many of which are beyond our control.
Our significant indebtedness, combined with our other financial obligations and contractual commitments, could
have important consequences on our business, including:
●
limiting our ability to obtain additional financing to fund future working capital, capital expenditures or other
general corporate purposes, including product development, commercialization efforts, research and
development activities, strategic arrangements, acquisitions and refinancing of our outstanding debt;
●
requiring a substantial portion of our cash flows to be dedicated to debt service payments instead of other
purposes, thereby reducing the amount of cash flows available for working capital, capital expenditures,
corporate transactions and other general corporate purposes;
●
increasing our vulnerability to adverse changes in general economic, industry and competitive conditions;
●
limiting our flexibility in planning for and reacting to changes in the industry in which we compete;
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●
placing us at a disadvantage compared to other, less leveraged competitors or competitors with comparable debt
at more favorable interest rates; and
●
increasing our cost of borrowing.
If we do not generate sufficient cash flows from operations or if future borrowings are not available to us in an
amount sufficient to service our indebtedness, including payments of principal when due on our outstanding indebtedness or,
in the case of our Convertible Senior Notes, in connection with a transaction involving us that constitutes a fundamental
change under the indentures governing the Convertible Senior Notes, or under our Revolving Credit Facility, or to fund our
liquidity needs, we may be forced to refinance all or a portion of our indebtedness on or before the maturity dates thereof, sell
assets, reduce or delay currently planned activities or curtail operations, seek to raise additional capital or take other actions.
We may not be able to execute any of these actions on commercially reasonable terms or at all. This, together with any of the
factors described above, could materially and adversely affect our business, financial condition and results of operations.
The capped call transactions entered into in connection with our Convertible Senior Notes may affect the value of our
Class A Common Stock.
In connection with the issuance of our Convertible Senior Notes, we entered into capped call transactions, or the
Capped Calls, with certain financial institutions. These transactions are expected generally to reduce the potential dilution
upon any conversion of our Convertible Senior Notes, as applicable, or offset any cash payments we are required to make in
excess of the principal amount of converted Convertible Senior Notes, as the case may be.
In connection with these transactions, the financial institutions likely purchased our Class A Common Stock in
secondary market transactions and entered into various OTC derivative transactions with respect to our Class A Common
Stock. These entities or their affiliates are likely to modify their hedge positions from time to time prior to conversion or
maturity of the Convertible Senior Notes by purchasing and selling shares of our Class A Common Stock or other instruments
they may wish to use in connection with such hedging. Any of these activities could adversely affect the value of our Class A
Common Stock and, as a result, the number of shares and the value of the Class A Common Stock noteholders will receive
upon conversion of the Convertible Senior Notes. In addition, under certain circumstances the counterparties have the right to
terminate the Capped Calls on terms set forth in the applicable confirmations, which may result in us not receiving all or any
portion of the anticipated benefit of the Capped Calls. If the price of our Class A Common Stock increases such that the hedge
transactions settle in our favor, we could also be exposed to credit risk related to the counterparties to the Capped Calls, which
would limit or eliminate the benefit of such transactions to us.
Our quarterly and annual operating results may fluctuate significantly.
Our operating results have been, and we expect they will continue to be, subject to frequent fluctuations. Our net
income (loss) and other operating results will be affected by numerous factors, including:
●
the level of underlying demand and price for our products in the countries in which they are approved;
●
retail chains’ and wholesalers’ buying patterns, pricing and reimbursement and inventory levels with respect to
our products;
●
the costs associated with commercializing our products in the U.S.;
●
the achievement and timing of milestone payments and royalties due or payable under our collaboration and
license agreements;
●
our execution of any collaboration, partnership, licensing or other strategic arrangements, and the timing of
payments we may make or receive under these arrangements;
●
any impairments of assets or goodwill, and associated write-downs;
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●
any variations in the level of expenses related to our development programs;
●
addition or termination of clinical trials;
●
results of or developments in nonclinical studies and clinical trials of our product candidates or those of our
competitors or potential collaborators;
●
any impact on taxes or changes in tax rules;
●
regulatory developments affecting our products and product candidates;
●
the success of competitive products or technologies;
●
any material lawsuit in which we may become involved;
●
general economic, industry, and market conditions; and
●
the impact of public health emergencies, including containment or mitigation measures, or natural disasters.
If our operating results fall below the expectations of investors or securities analysts for any of the foregoing reasons
or otherwise, the price of our Class A Common Stock could decline substantially. Furthermore, any quarterly or annual
fluctuations in our operating results may, in turn, cause the price of our stock to fluctuate substantially.
Our ability to use net operating loss and tax credit carryforwards and certain built-in losses to reduce future tax payments
is limited by provisions of the Internal Revenue Code, and it is possible that our net operating loss and tax credit
carryforwards may expire before we generate sufficient taxable income to use such carryforwards, or that certain
transactions or a combination of certain transactions may result in material additional limitations on our ability to use our
net operating loss and tax credit carryforwards.
For the year ended December 31, 2023, we incurred a net loss in connection with the VectivBio Acquisition. Prior to
the year ended December 31, 2019, we incurred significant net losses since our inception. To the extent that we do not
generate federal and state taxable income in the future, unused net operating loss and tax credit carryforwards will carry
forward to offset future taxable income, if any, until the date, if any, on which such unused carryforwards expire. Sections 382
and 383 of the Internal Revenue Code of 1986, as amended, contain rules that limit the ability of a company that undergoes an
ownership change, which is generally any change in ownership of more than 50% of its stock over a three-year period, to
utilize its net operating loss and tax credit carryforwards and certain built-in losses recognized in years after the ownership
change. These rules generally operate by focusing on ownership changes involving stockholders owning directly or indirectly
5% or more of the stock of a company and any change in ownership arising from a new issuance of stock by the company.
Generally, if an ownership change occurs, the yearly taxable income limitation on the use of net operating loss and tax credit
carryforwards and certain built-in losses is equal to the product of the applicable long-term tax exempt rate and the value of
the company’s stock immediately before the ownership change. Certain future equity offerings or strategic transactions, if any,
could potentially result in a 50% or greater change of control.
If we do not generate sufficient taxable income prior to the expiration, if any, of the applicable carryforwards or if the
carryforwards are subject to the limitations described above, we may be unable to offset our taxable income with losses, or our
tax liability with credits, before such losses and credits expire and therefore would incur larger federal or state income tax
liability. We have completed several financings since our inception which may have resulted in a change in control as defined
by Section 382, or could result in a change in control in the future.
Our ability to use foreign tax loss carryforwards acquired in the VectivBio Acquisition may be limited.
Prior to our acquisition of VectivBio, VectivBio incurred significant net losses since its inception. In Switzerland, tax
loss carryforwards may, with certain limitations, be used to offset future taxable income. However, if not utilized, the tax loss
carryforwards, under Swiss laws, expire seven years after the tax year in which they were incurred. Due to our current limited
income in Switzerland, there is a high risk that the tax loss carryforwards will expire
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in part or in their entirety and will not be used to offset future taxable income. Any limitations in our ability to use tax loss
carryforwards to offset taxable income could adversely affect our financial condition.
If the distribution of the shares of Cyclerion Therapeutics, Inc., or Cyclerion, common stock in connection with the
Separation is not generally tax- free for U.S. federal income tax purposes, we and our stockholders could be subject to
significant tax liabilities.
The distribution of the shares of Cyclerion common stock in connection with the Separation, together with certain
related transactions, is intended to qualify for tax-free treatment to us and our stockholders for U.S. federal income tax
purposes. We received a favorable private letter ruling from the Internal Revenue Service, or IRS, under the pilot program
established in Revenue Procedure 2017-52 relating to the U.S. federal income tax treatment of the distribution. Consistent
with the guidelines set forth in Revenue Procedure 2017-52, the IRS private letter ruling does not cover all of the issues that
are relevant to determining whether the distribution is generally tax free for U.S. federal income tax purposes. Accordingly,
completion of the distribution was conditioned upon, among other things, our receipt of an opinion from an outside tax advisor
that the distribution will qualify as a transaction that is generally tax-free to both us and our stockholders for U.S. federal
income tax purposes under Sections 355 and 368(a)(1)(D) of the Internal Revenue Code. The private letter ruling and opinion
were based on and relied on, among other things, certain facts and assumptions, as well as certain representations, statements
and undertakings from us and Cyclerion (including those relating to the past and future conduct of us and Cyclerion). If any of
these facts, assumptions, representations, statements or undertakings is, or becomes, inaccurate or incomplete, or if we or
Cyclerion breach any of our respective covenants relating to the distribution, the IRS private letter ruling and any tax opinion
may be invalid. Moreover, the opinion is not binding on the IRS or any courts. Accordingly, notwithstanding receipt of the
IRS private letter ruling and the opinion, the IRS could determine that the distribution and certain related transactions should
be treated as taxable transactions for U.S. federal income tax purposes.
If the distribution, together with certain related transactions, fails to qualify as a transaction that is generally tax-free
under Sections 355 and 368(a)(1)(D) of the Internal Revenue Code, in general, for U.S. federal income tax purposes, we
would recognize taxable gain with respect to Cyclerion’s distributed common stock and our stockholders who received shares
of Cyclerion common stock in the distribution would be subject to tax as if they had received a taxable distribution equal to
the fair market value of such shares.
General Risk Factors
We may not be able to manage our business effectively if we lose any of our current management team or if we are unable
to attract, motivate and retain key personnel.
We may not be able to attract, motivate or retain qualified management and scientific, clinical, operations and
commercial personnel due to the intense competition for qualified personnel among biotechnology, pharmaceutical and other
businesses, particularly in the greater-Boston area. If we are not able to attract, motivate and retain necessary personnel to
accomplish our business objectives, we will experience constraints that will significantly impede the achievement of our
objectives.
We are highly dependent on the drug research, development, regulatory, commercial, financial and other expertise of
our management, particularly Thomas McCourt, our chief executive officer; Gregory Martini, our senior vice president, chief
financial officer; John Minardo, our senior vice president, chief legal officer and secretary; and Michael Shetzline, our senior
vice president, chief medical officer and head of research and drug development. Transitions in our senior management team
or other key employees, or the unavailability of any such persons for any reason, can be inherently difficult to manage and
may disrupt our operations or business or otherwise harm our business, for example, due to the diversion of our board and
management’s time and attention and a decline in employee morale. In addition to the competition for personnel, the Boston
area in particular is characterized by a high cost of living. As such, we could have difficulty attracting experienced personnel
to our company and may be required to expend significant financial resources in our employee recruitment efforts, which may
or may not be successful.
We also have scientific and clinical advisors who assist us in formulating our product development, clinical strategies
and our global supply chain plans, as well as sales and marketing advisors who have assisted us in our commercialization
strategy and brand plan for our products. These advisors are not our employees and may have commitments to, or consulting
or advisory contracts with, other entities that may limit their availability to us, or may
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have arrangements with other companies to assist in the development and commercialization of products that may compete
with ours.
Security breaches and other disruptions to our information technology structure could compromise our information,
disrupt our business and expose us to liability, which would cause our business and reputation to suffer.
In the ordinary course of our business, we collect, process and store sensitive data, including intellectual property, our
proprietary business information and that of our suppliers and business partners, as well as personally identifiable information
of our patients, clinical trial participants and employees. We also rely to a large extent on information technology systems to
operate our business, including to deliver our products. We have outsourced elements of our confidential information
processing and information technology structure, and as a result, we are managing independent vendor relationships with third
parties who may or could have access to our confidential information. Similarly, our business partners and other third-party
providers possess certain of our sensitive data. The secure maintenance of this information is critical to our operations and
business strategy. Despite our security measures, our large and complex information technology and infrastructure (and those
of our partners, vendors and third-party providers) are vulnerable to attacks by hackers and may be breached due to employee,
partner, vendor or third-party error, malfeasance or other disruptions. We, our partners, vendors and other third-party providers
could be susceptible to third party attacks on our, and their, information security systems, which attacks are of ever-increasing
levels of sophistication and are made by groups and individuals with a wide range of motives and expertise, including
organized criminal groups, hacktivists, nation states and others. While we have invested in information technology and
security and the protection of confidential information, there can be no assurance that our efforts will prevent service
interruptions or security breaches. Further, while some or all of our workforce, and those of our partners, vendors and other
third-party providers, work remotely, we may have greater vulnerability to cyberattacks or other losses of confidential
information, as well as interruptions in information technology systems. Any such interruptions, losses or breaches would
substantially impair our ability to operate our business and would compromise our, or our partners, vendors and other third-
party providers, networks and the information stored there could be accessed, publicly disclosed, lost or stolen. Any such
access, disclosure or other loss of information could result in legal claims or proceedings, liability under laws that protect the
privacy of personal information, disrupt our operations, negatively impact our financial condition and damage our reputation,
any of which could adversely affect our business. While we maintain cyber liability insurance, this insurance may not be
sufficient to cover the financial or other losses that may result from an interruption or breach of our (or our partners’, vendors’
and third-party providers’) systems.
Anti-takeover provisions under our charter documents and Delaware law could delay or prevent a change of control which
could negatively impact the market price of our Class A Common Stock.
Provisions in our certificate of incorporation and bylaws may have the effect of delaying or preventing a change of
control. These provisions include the following:
●
Our board of directors has the right to elect directors to fill a vacancy created by the expansion of the board of
directors or the resignation, death or removal of a director, which prevents stockholders from being able to fill
vacancies on our board of directors.
●
Our board of directors may issue, without stockholder approval, shares of preferred stock. The ability to
authorize preferred stock makes it possible for our board of directors to issue preferred stock with voting or other
rights or preferences that could impede the success of any attempt to acquire us.
●
Stockholders must provide advance notice to nominate individuals for election to the board of directors or to
propose matters that can be acted upon at a stockholders’ meeting. These provisions may discourage or deter a
potential acquirer from conducting a solicitation of proxies to elect such acquirer’s own slate of directors or
otherwise attempting to obtain control of our company.
●
Our stockholders may not act by written consent. As a result, a holder, or holders, controlling a majority of our
capital stock are not able to take certain actions outside of a stockholders’ meeting.
●
Special meetings of stockholders may be called only by the chairman of our board of directors, our chief
executive officer or a majority of our board of directors. As a result, a holder, or holders, controlling a majority
of our capital stock are not able to call a special meeting.
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●
A super-majority (80%) of the outstanding shares of Class A Common Stock are required to amend our bylaws,
which make it more difficult to change the provisions described above.
In addition, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which may
prohibit certain business combinations with stockholders owning 15% or more of our outstanding voting stock. These and
other provisions in our certificate of incorporation and our bylaws and in the Delaware General Corporation Law could make
it more difficult for stockholders or potential acquirers to obtain control of our board of directors or initiate actions that are
opposed by the then-current board of directors.
We have identified material weaknesses in our internal control over financial reporting. If we are not able to remediate
these material weaknesses, or if we identify additional material weaknesses in the future, it could have an adverse effect on
our business and financial results, and our ability to meet our reporting obligations could be negatively affected, each of
which could negatively affect the trading price of our Class A Common Stock.
In connection with the audit of our consolidated financial statements for the year ended December 31, 2024, we and
our independent registered public accounting firm have identified material weaknesses in our internal control over financial
reporting and we determined that our internal control over financial reporting was not effective as of December 31, 2024. A
material weakness is a deficiency, or a combination of deficiencies, in internal control over financial reporting, such that there
is a reasonable possibility that a material misstatement of our annual or interim financial statements will not be prevented or
detected on a timely basis. Accordingly, a material weakness increases the risk that the financial information we report
contains material errors. For further discussion of the material weaknesses we have identified and our remediation plan, see
Part II, Item 9A, under the heading “Controls and Procedures” in this Annual Report on Form 10-K.
While we have designed and are implementing a remediation plan to remediate these material weaknesses, we cannot
assure that the measures we have taken to date, together with any measures we may take in the future, will be sufficient to
remediate the material weaknesses we have identified or avoid the identification of additional material weaknesses in the
future. If the steps we take do not remediate the material weaknesses in a timely manner, there could continue to be a
reasonable possibility that these control deficiencies or others could result in a material misstatement of our annual or interim
financial statements that would not be prevented or detected on a timely basis. If we are not able to remediate these material
weaknesses in a timely manner or otherwise comply with the requirements of Section 404 of the Sarbanes-Oxley Act in a
timely manner, our ability to record, process, summarize and report financial information accurately and within applicable
time periods may be adversely affected. If we are not able to remediate these material weaknesses in a timely manner,
investors could lose confidence in the reliability of our financial statements, which could lead to a decline in our stock price.
In addition, our conclusion that we have material weaknesses could give rise to increased scrutiny, review, audit and
investigation over our accounting controls and procedures.
We regularly review and update our internal controls, disclosure controls and procedures, and corporate governance
policies. In addition, we are required under the Sarbanes-Oxley Act of 2002 to report annually on our internal control over
financial reporting. Our system of internal controls, however well-designed and operated, is based in part on certain
assumptions and includes elements that rely on information from third parties, including our partners. Our system can provide
only reasonable, not absolute, assurances that the objectives of the system are met.
Further, we are dependent on our partners for information related to our results of operations. Our net profit or net
loss generated from the sales of LINZESS in the U.S. is partially determined based on amounts provided by AbbVie and
involves the use of estimates and judgments, which could be modified in the future. For example, during 2024, we recorded
adjustments to our collaborative arrangement revenues to reflect changes in estimates of certain LINZESS gross-to-net
reserves, as reported by AbbVie. We are highly dependent on our linaclotide partners for timely and accurate information
regarding any revenues realized from sales of linaclotide in their respective territories, and in the case of AbbVie for the U.S.,
the costs incurred in developing and commercializing it in order to accurately report our results of operations. Our results of
operations are also dependent on the timeliness and accuracy of information from any other licensing, collaboration or other
partners we may have, as well as our and our partners’ use of estimates and judgments. If we do not receive timely and
accurate information or if estimated activity levels associated with the relevant collaboration or partnership at a given point in
time are incorrect, whether the result of a material weakness or not, we could be required to record adjustments in future
periods. Such adjustments could have an adverse effect on our financial results, which could lead to a decline in our Class A
Common Stock price.
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If in the future we cannot conclude that we have effective internal control over our financial reporting, or if our
independent registered public accounting firm is unable to provide an unqualified opinion regarding the effectiveness of our
internal control over financial reporting, investors could lose confidence in the reliability of our financial statements, which
could lead to a decline in our stock price. Failure to comply with reporting requirements could also subject us to sanctions
and/or investigations by the SEC, The Nasdaq Stock Market or other regulatory authorities.
We expect that the price of our Class A Common Stock will fluctuate substantially.
The market price of our Class A Common Stock may be highly volatile due to many factors, including:
●
the commercial performance of our products in the countries in which they are approved, as well as the costs
associated with such activities;
●
any third-party coverage and reimbursement policies for our products;
●
market conditions in the pharmaceutical and biotechnology sectors;
●
developments, litigation or public concern about the safety of our products or our potential products;
●
announcements of the introduction of new products by us or our competitors;
●
announcements concerning product development, including clinical trial results or timelines, or intellectual
property rights of us or others;
●
actual and anticipated fluctuations in our quarterly and annual operating results;
●
deviations in our operating results from any guidance we may provide or the estimates of securities analysts;
●
sales of additional shares of our Class A Common Stock or sales of securities convertible into Class A Common
Stock or the perception that these sales might occur;
●
any conversions of our Convertible Senior Notes into Class A Common Stock or activities undertaken by the
counterparties to the Capped Calls;
●
additions or departures of key personnel;
●
developments concerning current or future collaboration, partnership, licensing or other strategic arrangements;
●
discussion of us or our stock price in the financial or scientific press or in online investor communities;
●
general economic, industry, and market conditions; and
●
the impact of public health epidemics, including containment or mitigation measures, or natural disasters.
Our business could be negatively affected as a result of a proxy contest or certain other stockholder actions.
Responding to certain stockholder actions can be costly, disruptive and time-consuming, and could also impact our
ability to attract, retain and motivate our employees. For example, a proxy contest for our annual meeting of stockholders
relating to stockholder proposals or director nominees would require significant time and could divert the attention of our
management, other employees and our board of directors. In addition, a proxy contest would require us to incur significant
costs, including legal fees and proxy solicitation expenses.
The realization of any of the risks described in these “Risk Factors” could have a dramatic and material adverse
impact on the market price of our Class A Common Stock. In addition, class action litigation has often been instituted
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against companies whose securities have experienced periods of volatility. Any such litigation brought against us could result
in substantial costs and a diversion of management attention, which could hurt our business, operating results and financial
condition.
Item 1B. Unresolved Staff Comments
None.
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Item 1C. Cybersecurity
We have a multilayered framework for assessing, identifying, detecting and responding to reasonably foreseeable
cybersecurity risks and threats. To protect our information technology, or IT, systems from cybersecurity threats, we use
various security tools that help prevent, identify, escalate, investigate, resolve and recover from identified vulnerabilities and
security incidents in a timely manner. In the event of a material change to our systems or operations, we would conduct an
assessment of the internal and external threats to the security, confidentiality, integrity, and availability of our data and
systems, along with other material risks to our operations. We leverage third-party security services for audit, benchmarking,
and improvement and use various tools and methodologies to manage cybersecurity risks that are tested regularly, including a
cybersecurity assessment guided by the National Institute of Standards and Technology (NIST) cybersecurity framework and
ongoing security awareness training. We oversee third-party service providers by conducting vendor diligence upon
onboarding and ongoing monitoring. Vendors are assessed for risk based on the nature of their digital footprint, company
profile, domain name services health, internet protocol reputation, external access threats and social engineering landscapes,
based on that assessment, we conduct diligence that may include completing security questionnaires, onsite evaluation, and
scans or other technical evaluations. We also monitor and evaluate our cybersecurity posture and performance on an ongoing
basis through regular vulnerability scans, simulated phishing tests, penetration tests, and threat intelligence feeds. The results
of these assessments are reported to the Audit Committee of the Board of Directors.
We have developed an incident response plan designed to coordinate the activities that we and our third-party service
providers take to prepare to respond and recover from cybersecurity incidents, which include processes to triage, assess
severity, investigate, escalate, contain, and remediate an incident, as well as to comply with potentially applicable legal
obligations and mitigate any reputational damage.
Our business strategy, results of operations and financial condition have not been materially affected as a result of
previously identified cybersecurity incidents, but we cannot provide assurance that they will not be materially affected in the
future by such cybersecurity risks or any future material incidents. For more information on our cybersecurity-related risks,
see Item 1A, Risk Factors, elsewhere in this Annual Report on Form 10-K.
The Company’s Senior Vice President, Controller and Principal Accounting Officer is responsible for managerial
oversight of our cybersecurity program and reporting on cybersecurity matters to the Audit Committee of the Board of
Directors and management. Our Senior Vice President, Controller and Principal Accounting Officer oversees the cybersecurity
team, which include members of our internal IT department and is also supported by third-party service providers.
Our Board of Directors is responsible for overseeing our enterprise risk management activities in general, and each of
our Board committees assists the Board in the role of risk oversight. The Audit Committee of the Board of Directors oversees
our cybersecurity risk and receives regular reports, with a minimum frequency of once per year, from our Senior Vice
President, Controller and Principal Accounting Officer on various cybersecurity matters, including risk assessments,
mitigation strategies, areas of emerging risks, incidents and industry trends, and other areas of importance. Promptly after
becoming aware of a material cybersecurity incident affecting our IT systems or data, the Audit Committee would work with
management to formulate a mitigation plan and review compliance with such plan, as well as to ensure compliance with any
external regulatory or disclosure requirements, including any disclosures of material cybersecurity breaches.
Item 2. Properties
Our corporate headquarters are located in Boston, Massachusetts, where, as of December 31, 2024, we occupied
approximately 39,000 square feet of office space under our lease expiring in June 2030. We also have operations in Basel,
Switzerland. We believe that our facilities are suitable and adequate for our needs for the foreseeable future.
Item 3. Legal Proceedings
None.
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Item 4. Mine Safety Disclosures
Not applicable.
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PART II
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities
Shares of our Class A Common Stock are traded on the Nasdaq Global Select Market under the symbol “IRWD.” Our
shares have been publicly traded since February 3, 2010. As of January 31, 2025, there were 29 stockholders of record of our
Class A Common Stock. The number of record holders is based upon the actual number of holders registered on the books of
the company at such date and does not include holders of shares in “street names” or persons, partnerships, associations,
corporations or other entities identified in security position listings maintained by depositories.
Subject to preferences that may apply to any shares of preferred stock outstanding at the time, the holders of Class A
Common Stock are entitled to share equally in any dividends that our board of directors may determine to issue from time to
time. In the event a dividend is paid in the form of shares of common stock or rights to acquire shares of common stock, the
holders of Class A Common Stock will receive Class A Common Stock, or rights to acquire Class A Common Stock, as the
case may be.
We have never declared or paid any cash dividends on our capital stock, and we do not currently anticipate declaring
or paying cash dividends on our capital stock in the foreseeable future. We currently intend to retain all of our future earnings,
if any, to finance operations and any acquisitions of businesses, products and technologies or other strategic transactions. Any
future determination relating to our dividend policy will be made at the discretion of our board of directors and will depend on
a number of factors, including future earnings, capital requirements, financial conditions, future prospects, contractual
restrictions and covenants and other factors that our board of directors may deem relevant.
The information required to be disclosed by Item 201(d) of Regulation S-K, “Securities Authorized for Issuance
Under Equity Compensation Plans,” is referenced under Item 12 of Part III of this Annual Report on Form 10-K.
Corporate Performance Graph
The following performance graph and related information shall not be deemed to be “soliciting material” or to be
“filed” with the SEC, nor shall such information be incorporated by reference into any future filing under the Securities Act of
1933, as amended, except to the extent that we specifically incorporate it by reference into such filing.
The following graph compares the performance of our Class A Common Stock to the Nasdaq U.S. Benchmark Index
and to the Nasdaq Biotechnology Index from December 31, 2019 through December 31, 2024. The comparison assumes $100
was invested after the market closed on December 31, 2019 in our Class A Common Stock and in each of the presented
indices, and it assumes reinvestment of dividends, if any. The stock price performance included in this graph is not necessarily
indicative of future stock price performance.
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COMPARISON OF 5-YEAR CUMULATIVE TOTAL RETURN
Among The Nasdaq U.S. Benchmark Index,
the Nasdaq Biotechnology Index,
and Ironwood Pharmaceuticals, Inc.
Item 6. [Reserved]
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Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations
The following discussion of our financial condition and results of operations should be read in conjunction with our
consolidated financial statements and the notes to those financial statements appearing elsewhere in this Annual Report on
Form 10-K. This discussion contains forward-looking statements that involve significant risks and uncertainties. As a result of
many factors, such as those set forth under “Risk Factors” in Item 1A of this Annual Report on Form 10-K, our actual results
may differ materially from those anticipated in these forward-looking statements.
Discussion and analysis of our financial condition and results of operations for the fiscal year ended December 31,
2023 compared to the fiscal year ended December 31, 2022 is included in Part II, Item 7 – "Management's Discussion and
Analysis of Financial Condition and Results of Operations" in our Annual Report on Form 10-K for the fiscal year ended
December 31, 2023 filed with the SEC on February 16, 2024.
Overview
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.
LINZESS® (linaclotide), our commercial product, is the first product approved by the U.S. FDA, in a class of GI
medicines called GC-C agonists and is indicated for adult men and women suffering from IBS-C or CIC, and for pediatric
patients ages 6-17 years-old suffering from FC. LINZESS is available to adult men and women suffering from IBS-C or CIC
in 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 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 in the U.S. and all countries worldwide other
than China (including Hong Kong and Macau) and Japan, AstraZeneca in China (including Hong Kong and Macau), and
Astellas in Japan.
We also aim to leverage our development and commercialization capabilities in GI to bring additional treatment
options to GI patients.
Through the VectivBio Acquisition, we are advancing apraglutide, a next-generation, synthetic long-acting peptide
analog of GLP-2 for SBS patients who are dependent on 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 NDA submission
to the U.S. FDA and plan to submit marketing applications to other regulatory authorities for apraglutide for use in adult
patients with SBS who are dependent on PS.
In November 2021, we entered into the COUR Collaboration Agreement with COUR, that granted us an option to
acquire an exclusive license to research, develop, manufacture and commercialize, in the U.S., products containing CNP-104,
a tolerizing immune modifying nanoparticle, for the treatment of PBC. 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, the 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
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.
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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 our other product candidates, including apraglutide. Prior to the year
ended December 31, 2019, we incurred net losses in each year since inception. As of December 31, 2024, we had an
accumulated deficit of approximately $1.7 billion. We are unable to predict the extent of any future losses or guarantee that
our company will be able to maintain positive cash flows.
We were incorporated in Delaware on January 5, 1998 as Microbia, Inc. On April 7, 2008, we changed our name to
Ironwood Pharmaceuticals, Inc. We operate in one reportable business segment – human therapeutics.
Key 2024 Financial Highlights
●
We recognized $351.4 million in total revenues during the year ended December 31 2024, compared to $442.7
million during the year ended December 31, 2023. The decrease was primarily related to a $90.1 million
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.
●
We generated income from operations of $93.1 million during the year ended December 31, 2024 compared to a
loss from operations of $945.4 million during the year ended December 31, 2023. The increase was primarily
attributable to incurring approximately $1.1 billion in IPR&D expense related to the VectivBio Acquisition in
2023.
●
We generated $103.5 million in cash from operations during the year ended December 31, 2024, ending the year
with $88.6 million in cash and cash equivalents.
Financial Operations Overview
Revenues. Our revenues are generated primarily through our collaborative arrangements and license agreements
related to research and development and commercialization of linaclotide.
The majority of our revenues are generated from the sales of LINZESS in the U.S. We record our share of the net
profits and losses from the sales of LINZESS in the U.S. less commercial expenses on a net basis and present the settlement
payments to and from AbbVie as collaboration expense or collaborative arrangements revenue, as applicable. Net profits or
losses consist of net sales to third-party customers and sublicense income in the U.S. less the cost of goods sold as well as
selling, general and administrative expenses. Although we expect net sales to increase over time, the settlement payments
between AbbVie and us, resulting in collaborative arrangements revenue or collaboration expense, are subject to fluctuation
based on the ratio of selling, general and administrative expenses incurred by each party. In addition, our collaborative
arrangements revenue may fluctuate as a result of the timing and amount of license fees and clinical and commercial
milestones received and recognized under our current and future strategic partnerships as well as timing and amount of
royalties from the sales of linaclotide in the European, Canadian, Mexican, Japanese, or Chinese markets or any other markets
where linaclotide receives approval and is commercialized.
Cost of Revenues. Cost of revenues primarily includes costs related to the sales of linaclotide API, finished drug
product, and finished goods to our partners, which generally occurs upon shipment for sales of API, finished drug product and
finished goods after the material has passed all quality testing required for acceptance by the partner to certain of our partners
outside of the U.S.
Research and Development Expense. The core of our research and development strategy is to leverage our
demonstrated expertise and capabilities in GI diseases to bring multiple medicines to patients. Research and development
expense consists of expenses incurred in connection with the research into and development of products and product
candidates. These expenses consist primarily of compensation, benefits and other employee-related expenses, research and
development related facility costs, third-party contract costs relating to nonclinical study and clinical trial activities,
development of manufacturing processes, regulatory registration of third-party manufacturing facilities, and licensing fees for
our product candidates.
Research and development expenses include amounts owed to AbbVie on an ongoing basis under cost-sharing
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provisions in our collaboration agreement for linaclotide. Reimbursements received for research and development activities
under this agreement are netted against research and development expenses.
Linaclotide. Our commercial product, LINZESS, is commercially available in the U.S. for the treatment of IBS-C or
CIC in adults and for FC in pediatric patients ages 6-17 years-old. Linaclotide is also available to adult men and women
suffering from IBS-C or CIC in certain countries of the world, including China, Japan, and in a number of European countries.
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. In September 2020,
based on the Phase IIIb data of linaclotide 290 mcg on the overall abdominal symptoms of bloating, pain and discomfort in
adult patients with IBS-C, the U.S. FDA approved our sNDA to include a more comprehensive description of the effects of
LINZESS in its approved label.
In addition, we and AbbVie have established a nonclinical and clinical post-marketing plan with the U.S. FDA to
understand the safety and efficacy of LINZESS in pediatric patients. In August 2021, the U.S. FDA approved a revised label
for LINZESS based on clinical safety data that had been generated thus far in pediatric studies. The updated label modified the
boxed warning for risk of serious dehydration and contraindication against use in children to those less than two years of age.
The boxed warning and contraindication previously applied to all children less than 18 years of age and less than 6 years of
age, respectively. 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.
Apraglutide for SBS-IF. 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. SBS-IF, a rare and severe organ failure condition in which patients are dependent on PS, affects an
estimated 18,000 adult patients in the U.S., Europe, and Japan. 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 to the U.S. FDA and plan to submit marketing applications to other regulatory filings for apraglutide for use in
adult patients with SBS who are dependent on PS.
Apraglutide for aGvHD. In March 2024, we announced positive, primary results up to Day 91 for our Phase II
exploratory trial, STARGAZE, to evaluate apraglutide in patients with steroid-refractory GI aGvHD, 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.
CNP-104. Through the COUR Collaboration Agreement, we and COUR were developing CNP-104 for the treatment
of 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, the COUR Collaboration Agreement has
terminated, and we retain no rights and have no obligations related to CNP-104.
IW-3300. 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 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.
IW-3718. We were developing IW-3718, a gastric retentive formulation of a bile acid sequestrant, for the potential
treatment of refractory GERD. In September 2020, we announced that one of our two identical Phase III trials evaluating IW-
3718 in refractory GERD did not meet the pre-specified criteria associated with a planned early efficacy assessment and,
based on these findings, we discontinued development of IW-3718.
Early research and development. Our early research and development efforts have been focused on supporting our
development stage GI programs, including exploring strategic options for further development of certain of our internal
programs, as well as evaluating external development-stage GI programs.
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The following table sets forth our research and development expenses related to our product pipeline for the years
ended December 31, 2024, 2023, and 2022, respectively. These expenses relate primarily to compensation, benefits and other
employee-related expenses and external costs associated with nonclinical studies and clinical trial costs for our product
candidates. We allocate costs related to facilities, depreciation, share-based compensation, research and development support
services and certain other costs directly to programs.
Year Ended December 31,
2024
2023
2022
Linaclotide(1)
$ 17,858
$
21,103
$
17,267
Apraglutide(2)
73,008
58,244
—
IW-3718
—
—
461
IW-3300
13,179
15,091
15,824
CNP-104(3)
4,253
9,461
1,022
Early research and development(4)
3,123
12,186
9,691
Total research and development expenses
$ 111,421
$
116,085
$
44,265
(1)
Includes linaclotide in all indications, populations and formulations.
(2)
Includes $11.4 million of share-based compensation expense and $3.5 million of employer payroll tax expense recognized immediately after the closing
of the VectivBio Acquisition in the second quarter of 2023 in connection with the vesting acceleration and settlement of outstanding stock options and
restricted stock units.
(3)
Includes $6.0 million up-front payment recognized in the second quarter of 2023 in connection with the amendment to the COUR Collaboration
Agreement.
(4)
Includes $4.8 million reduction to research and development expense recognized in the first quarter of 2024 in connection with the settlement of a
license-related contract liability.
The lengthy process of securing regulatory approvals for product candidates, including apraglutide, requires the
expenditure of substantial resources. Any failure by us to obtain, or any delay in obtaining, regulatory approvals would
materially adversely affect our product development efforts and our business overall.
We and AbbVie are exploring development opportunities to enhance the clinical profile of LINZESS by studying
linaclotide in additional indications, populations and formulations to assess its potential to treat various conditions. We cannot
currently estimate with any degree of certainty the amount of time or money that we will be required to expend in the future
on linaclotide for additional indications, populations or formulations.
Given the inherent uncertainties that come with the development of pharmaceutical products, we cannot estimate
with any degree of certainty how our programs will evolve, and therefore the amount of time or money that would be required
to obtain regulatory approval to market them.
As a result of these uncertainties surrounding the timing and outcome of any approvals, we are currently unable to
estimate precisely when, if ever, linaclotide’s utility will be expanded within its currently approved indications; if or when
linaclotide will be developed outside of its current markets, indications, populations or formulations; or when, if ever,
apraglutide or any of our other product candidates will generate revenues and cash flows.
We invest carefully in our pipeline, and the commitment of funding for each subsequent stage of our development
programs is dependent upon the receipt of clear, supportive data. In addition, we intend to access externally discovered drug
candidates that fit within our core strategy. In evaluating these potential assets, we apply the same investment criteria as those
used for investments in internally discovered assets.
The successful development of our product candidates is highly uncertain and subject to a number of risks including,
but not limited to:
●
The duration of clinical trials may vary substantially according to the type, complexity and novelty of the
product candidate;
●
The U.S. FDA and comparable foreign agencies impose substantial and varying requirements on the
introduction of therapeutic pharmaceutical products, typically requiring lengthy and detailed laboratory and
clinical testing procedures, sampling activities and other costly and time-consuming procedures;
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●
Data obtained from nonclinical and clinical activities at any step in the testing process may be adverse and lead
to discontinuation or redirection of development activity. Data obtained from these activities also are susceptible
to varying interpretations, which could delay, limit or prevent regulatory approval;
●
The duration and cost of early research and development, including nonclinical studies and clinical trials, may
vary significantly over the life of a product candidate and are difficult to predict;
●
The costs, timing and outcome of regulatory review of a product candidate may not be favorable, and, even if
approved, a product may face post-approval development and regulatory requirements;
●
There may be substantial costs, delays and difficulties in successfully integrating externally developed product
candidates into our business operations; and
●
The emergence of competing technologies and products and other adverse market developments may negatively
impact us.
As a result of the factors discussed above, including the factors discussed under “Risk Factors” in Item 1A of this
Annual Report on Form 10-K, we are unable to determine the duration and costs to complete current or future nonclinical and
clinical stages of our product candidates or when, or to what extent, we will generate revenues from the commercialization
and sale of our product candidates. Development timelines, probability of success and development costs vary widely. We
anticipate that we will make determinations as to which additional programs to pursue and how much funding to direct to each
program on an ongoing basis in response to the data of each product candidate, the competitive landscape and ongoing
assessments of such product candidate’s commercial potential.
We expect to invest in our development programs and incur substantial research and development expenses for the
foreseeable future. We will continue to invest in linaclotide, including the investigation of ways to enhance the clinical profile
within its currently approved indications, and the exploration of its potential utility in other indications, populations and
formulations. We will continue to invest in our GI and rare disease-focused product candidates, including apraglutide, as we
advance them through pre-clinical and clinical trials, in addition to funding research and development activities under our
external collaboration and license agreements.
Acquired In-Process Research and Development. Asset acquisition costs, license fees and development milestone
payments related to acquired and in-licensed products and technology are expensed as acquired in-
process research and development at the point that they have no established alternative future use.
Selling, General and Administrative Expense. Selling, general and administrative expense consists primarily of
compensation, benefits and other employee-related expenses for personnel in our administrative, finance, legal, information
technology, business development, commercial, sales, marketing, communications and human resource functions. Other costs
include legal costs of pursuing patent protection of our intellectual property, general and administrative related facility costs,
insurance costs and professional fees for accounting, tax, consulting, legal and other services. As we continue to invest in the
development and commercialization of LINZESS, apraglutide and other product candidates, we expect our selling, general
and administrative expenses will be substantial for the foreseeable future.
We include AbbVie’s selling, general and administrative cost-sharing payments in the calculation of the net profits
and net losses from the sale of LINZESS in the U.S. and present the net payment to or from AbbVie as collaboration expense
or collaborative arrangements revenue, respectively.
Restructuring Expenses. Restructuring expenses pertain to a headquarters-based workforce reduction in April 2023
and restructuring initiatives in connection with the VectivBio Acquisition commencing in June 2023. The workforce reduction
and restructuring initiatives are more fully described in Note 16, Workforce Reductions and Restructuring, to our consolidated
financial statements appearing elsewhere in this Annual Report on Form 10-K.
Interest Expense and Other Financing Costs. Interest expense consists primarily of cash and non-cash interest costs
related to our convertible senior notes and Revolving Credit Facility. Non-cash interest expense consists of amortization of
debt issuance costs.
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Interest and Investment Income. Interest and investment income consists of interest earned on our cash and cash
equivalents, as well as significant financing components of payments due from collaboration partners.
Gain on Derivatives. In June 2015, we issued 2.25% Convertible Senior Notes due June 15, 2022, or the 2022
Convertible Notes, and in August 2019, we issued the Convertible Senior Notes. In connection with the issuance of our 2022
Convertible Notes, we entered into note hedge warrant transactions, or the Note Hedge Warrants, with certain financial
institutions. Gain on derivatives consists of the change in fair value of the Note Hedge Warrants, which are recorded at fair
value at each reporting date and changes in fair value are recorded in our consolidated statements of income (loss). The Note
Hedge Warrants terminated unexercised upon expiry in April 2023. The Note Hedge Warrants are more fully described in Note
10, Debt, to our consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K.
Income Taxes. We prepare our income tax provision based on our interpretation of the income tax accounting rules
and each jurisdiction’s enacted tax laws and regulations. For additional information refer to Note 14, Income Taxes, to our
consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K.
Critical Accounting Policies and Estimates
Our discussion and analysis of our financial condition and results of operations is based upon our consolidated
financial statements prepared in accordance with U.S. generally accepted accounting principles. The preparation of these
financial statements requires us to make certain estimates and assumptions that may affect the reported amounts of assets and
liabilities, the disclosure of assets and liabilities at the date of the consolidated financial statements, and the amounts of
revenues and expenses during the reported periods. We base our estimates on our historical experience and on various other
assumptions that are believed to be reasonable, the results of which form the basis for making judgments about the carrying
values of assets and liabilities. Actual results may differ materially from our estimates under different assumptions or
conditions. Changes in estimates are reflected in reported results in the period in which they become known.
We believe that our application of the following accounting policies, each of which require significant judgments and
estimates on the part of management, are the most critical to aid in fully understanding and evaluating our reported financial
results. Our significant accounting policies are more fully described in Note 2, Summary of Significant Accounting Policies, to
our consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K.
Acquisitions
We evaluate acquisitions of assets and other similar transactions to assess whether the transaction should be
accounted for as a business combination or asset acquisition by first applying a screen test to determine whether substantially
all of the fair value of the gross assets acquired is concentrated into a single identifiable asset or group of similar identifiable
assets. If the screen test is met, a single asset or group of assets is not a business and is accounted for as an asset acquisition. If
the screen test is not met, further determination is required as to whether we have acquired inputs and processes that have the
ability to create outputs that would meet the requirements of a business.
We account for business combinations using the acquisition method of accounting, which requires the acquiring
entity to recognize the fair value of assets acquired and liabilities assumed and establishes the acquisition date as the fair value
measurement point. We determine the fair value of assets acquired and liabilities assumed based on management’s estimate of
the fair value of assets acquired and liabilities assumed in the acquisition. Goodwill represents the excess of the purchase price
over the fair value of the net tangible and intangible assets acquired. Transaction costs are expensed as incurred.
We account for asset acquisitions that are not determined to be a business combination by recognizing net assets
based on the consideration paid, inclusive of transaction costs, on a relative fair value basis. In an asset acquisition, the cost
allocated to acquired IPR&D with no alternative future use is charged to research and development expense at the acquisition
date. We classify asset acquisitions of acquired IPR&D as investing activities on its consolidated statements of cash flows.
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Revenue Recognition
Upon executing a revenue generating arrangement, we assess whether it is probable we will collect consideration in
exchange for the good or service it transfers to the customer and perform the following five steps: (i) identify the contract(s)
with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price; (iv) allocate the
transaction price to the performance obligations in the contract; and (v) recognize revenue when (or as) we satisfy the
performance obligations. We must develop assumptions that require significant judgment to determine the standalone selling
price for each performance obligation identified in the contract. The assumptions that are used to determine the standalone
selling price may include forecasted revenues, development timelines, reimbursement rates for personnel costs, discount rates
and probabilities of technical and regulatory success.
Our revenues are generated primarily through collaborative arrangements and license agreements related to the
development and commercialization of linaclotide. The terms of the collaborative arrangements and other agreements contain
multiple performance obligations which may include (i) licenses, (ii) research and development activities, including
participation on joint steering committees, (iii) the manufacture of finished drug product, API, or development materials for a
partner, which are reimbursed at a contractually determined rate, and (iv) education or co-promotion activities by our clinical
sales specialists. Non-refundable payments to us under these agreements may include (i) up-front license fees, (ii) payments
for research and development activities, (iii) payments for the manufacture of finished drug product, API, or development
materials, (iv) payments based upon the achievement of certain milestones, (v) payments for sales detailing, promotional
support services and medical education initiatives, and (vi) royalties on product sales. Additionally, we receive our share of the
net profits or bear our share of the net losses from the sale of linaclotide in the U.S. We have adopted a policy to recognize
revenue net of tax withholdings, as applicable.
Collaboration, License, and Other Agreements
Upon licensing intellectual property, we determine if the license is distinct from the other performance obligations
identified in the arrangement. We recognize revenues from the transaction price, including non-refundable, up-front fees
allocated to the license when the license is transferred to the customer if the license has distinct benefit to the customer. For
licenses that are combined with other promises, we assess the nature of the combined performance obligation to determine
whether the combined performance obligation is satisfied over time or at a point in time. For performance obligations that are
satisfied over time, we evaluate the measure of progress each reporting period and, if necessary, adjust the measure of
performance and related revenue recognition.
Our license and collaboration agreements include milestone payments, such as development and other milestones.
We evaluate whether the milestones are considered probable of being reached and estimate the amount to be included in the
transaction price using the most likely amount method at the inception of the agreement. If it is probable that a significant
revenue reversal would not occur, the associated milestone value is included in the transaction price. Milestone payments that
are not within our control, such as regulatory approvals, are not considered probable of being achieved until those approvals
are received. The transaction price is then allocated to each performance obligation on a relative standalone selling price basis,
for which we recognize revenue as or when the performance obligations under the contract are satisfied. We re-evaluate the
probability of achievement of such milestones and any related constraint at each reporting period, and any adjustments are
recorded on a cumulative catch-up basis.
Agreements that include the supply of API or drug product for either clinical development or commercial supply at
the customer’s discretion are generally considered as options. We assess if these options provide a material right to our partner,
and if so, they are accounted for as separate performance obligations. If we are entitled to additional payments when the
customer exercises these options, any additional payments are recorded as revenue when the customer obtains control of the
goods, which is typically upon shipment for sales of API and finished drug product.
For agreements that include sales-based royalties, including milestone payments based on the level of sales, and the
license is deemed to be the predominant item to which the royalties relate, we recognize revenue when the related sales occur
in accordance with the sales-based royalty exception.
Net Profit or Net Loss Sharing
In accordance with Accounting Standards Codification, or ASC, Topic 808, Collaborative Arrangements, or ASC
808, we considered the nature and contractual terms of the arrangement and the nature of our business operations to determine
the classification of payments under our collaboration agreements. While ASC 808 provides guidance on classification, the
standard is silent on matters of separation, initial measurement, and recognition. Therefore, we apply
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the separation, initial measurement, and recognition principles of ASC Topic 606, Revenue from Contracts with Customers, to
our collaboration agreements.
Our collaborative arrangements revenue generated from sales of LINZESS in the U.S. are considered akin to sales-
based royalties. We recognize our share of the pre-tax commercial net profit or net loss generated from the sales of LINZESS
in the U.S. in the period the product sales are earned, as reported by AbbVie, and related cost of goods sold and selling,
general and administrative expenses as incurred by us and our collaboration partner. These amounts are partially determined
based on amounts provided by AbbVie and involve the use of estimates and judgments, such as product sales allowances and
accruals related to prompt payment discounts, chargebacks, governmental and contractual rebates, wholesaler fees, product
returns, and co-payment assistance costs, which could be adjusted based on actual results in the future. We are highly
dependent on AbbVie for timely and accurate information regarding any net revenues realized from sales of LINZESS in the
U.S. in accordance with ASC 808, and the related costs, in order to accurately report its results of operations. If we do not
receive timely and accurate information or incorrectly estimate activity levels associated with the collaboration at a given
point in time, we could be required to record adjustments in future periods.
We record revenue transactions as net product revenue in our consolidated statements of income if we are deemed the
principal in the transaction, which includes being the primary obligor, retaining inventory risk, and control over pricing. Given
that we are not the primary obligor and do not have the inventory risks in the collaboration agreement with AbbVie for North
America, we record our share of the net profits or net losses from the sales of LINZESS in the U.S. on a net basis and present
the settlement payments to and from AbbVie as collaboration expense or collaborative arrangements revenue, as applicable.
We and AbbVie settle the cost sharing quarterly, such that our consolidated statements of income reflect 50% of the pre-tax net
profit or loss generated from sales of LINZESS in the U.S.
Deferred Revenue
Our deferred revenue balance consists of advance billings and payments received from customers in excess of
revenue recognized.
Research and Development Expense
We have committed significant resources into the research and development of our product candidates and intend to
continue to do so for the foreseeable future. Research and development expenses are generally expensed as incurred. We
capitalize nonrefundable advance payments we make for research and development activities and defer expense recognition
until the related goods are received or the related services are performed.
Research and development expenses are comprised of costs incurred in performing research and development
activities, including salary, benefits, share-based compensation, and other employee-related expenses; laboratory supplies and
other direct expenses; facilities expenses; overhead expenses; third-party contractual costs relating to nonclinical studies and
clinical trial activities and related contract manufacturing expenses, development of manufacturing processes and regulatory
registration of third-party manufacturing facilities; licensing fees for our product candidates; and other outside expenses.
Clinical trial expenses include expenses associated with CROs. The invoicing from CROs for services rendered can
lag several months. We accrue the cost of services rendered in connection with CRO activities based on our estimate of site
management, monitoring costs, project management costs, and investigator fees. We maintain regular communication with our
CRO vendors to gauge the reasonableness of our estimates. Differences between actual clinical trial expenses and estimated
clinical trial expenses recorded have not been material and are adjusted for in the period in which they become known.
However, if we incorrectly estimate activity levels associated with the CRO services at a given point in time, we could be
required to record material adjustments in future periods. Under our collaboration agreement with AbbVie for North America,
we are reimbursed for certain research and development expenses and we net these reimbursements against our research and
development expenses as incurred.
Research and development expenses also include up-front payment, non-contingent payment, and milestone payment
obligations under certain collaboration arrangements. Recognition of expense for such payments requires judgment with
respect to when the obligation is probable.
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Share-Based Compensation Expense
We grant awards under our share-based compensation programs, including stock awards, restricted stock awards, or
RSAs, restricted stock units, or RSUs (including performance-based RSUs, or PSUs), stock options, and shares issued under
our employee stock purchase plan, or ESPP. Share-based compensation is recognized as expense in the consolidated
statements of income based on the grant date fair value over the requisite service period, net of estimated forfeitures. We
estimate forfeitures over the requisite service period using historical forfeiture activity and record share-based compensation
expense only for those awards that are expected to vest.
We estimate the fair value of stock options on the date of grant using the Black-Scholes option-pricing model, which
requires the use of subjective assumptions including volatility and expected term, among others. The fair value of stock
awards, RSAs, and RSUs is based on the market value of our Class A Common Stock on the date of grant, with the exception
of PSUs with market conditions, which are measured using the Monte Carlo simulation method. Discounted stock purchases
under our ESPP are valued on the first date of the offering period using the Black-Scholes option-pricing model to compute
the fair value of the lookback provision plus the purchase discount.
For awards that vest based on service conditions and market conditions, we use the straight-line method to recognize
compensation expense over the respective service period. For awards that contain performance conditions, we determine the
appropriate amount to expense based on the anticipated achievement of performance targets, which requires judgment,
including forecasting the achievement of future specified targets. At the date performance conditions are determined to be
probable of achievement, we record a cumulative expense catch-up, with remaining expense amortized over the remaining
service period. Throughout the performance period, we re-assess the estimated performance and update the number of
performance-based awards that we believe will ultimately vest. Discounted stock purchases under our ESPP are recognized
over the offering period.
Compensation expense related to modified awards is measured based on the fair value for the awards as of the
modification date. Any incremental compensation expense arising from the excess of the fair value of the awards on the
modification date compared to the fair value of the awards immediately before the modification date is recognized at the
modification date or ratably over the remaining service period, as appropriate.
While the assumptions used to calculate and account for share-based compensation awards represent management’s
best estimates, these estimates involve inherent uncertainties and the application of management’s judgment. As a result, if
revisions are made to our underlying assumptions and estimates, our share-based compensation expense could vary
significantly from period to period.
Income Taxes
We use the asset and liability method of accounting for income taxes. Under this method, deferred tax assets and
liabilities are determined based on the difference between the financial statement carrying amounts and tax basis of assets and
liabilities using enacted tax rates in effect for years in which the temporary differences are expected to reverse.
At each quarterly reporting date, we reassess the valuation allowance on our deferred tax assets, weighing positive
and negative evidence to assess the recoverability of the deferred tax assets. We provide a valuation allowance when it is more
likely than not that deferred tax assets will not be realized. Our valuation allowance is comprised primarily of certain tax
credits that are expected to expire prior to utilization.
Significant judgment is required in making these assessments to maintain or reverse our valuation allowances and, to
the extent our future expectations change we would have to assess the recoverability of these deferred tax assets at that time. If
we determine that our net deferred tax assets are not realizable in a future period, we would record material changes to income
tax expense or benefit in that period.
We record uncertain tax positions on the basis of a two-step process. First, we determine whether it is more likely
than not that the tax positions will be sustained based on the technical merits of the position. Second, for those tax positions
that meet the more-likely-than-not recognition threshold, we recognize the largest amount of tax benefit that is greater than 50
percent likely to be realized upon ultimate settlement with the relevant tax authority. Significant judgment is required in
evaluating whether our tax positions meet this two-step process. The nature of the uncertain tax
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positions is often complex and subject to change, and the amounts at issue can be substantial. We re-evaluate these uncertain
tax positions on a quarterly basis based on a number of factors including, but not limited to, changes in facts or circumstances,
changes in tax law, and effectively settled issues under audit and new audit activity. Any change in these factors could result in
the recognition of a tax benefit or an additional charge to the tax provision.
Defined Benefit Pension Plan
Determining pension expense and obligations for our defined benefit pension plan uses actuarial estimates of
participants’ age at retirement, life span, the long-term rate of return on investments and other factors. In addition, pension
expense is sensitive to the discount rate used to value the pension obligation. As a sensitivity measure, an increase or decrease
in our discount rate assumption of 1.00% would decrease and increase our pension expense by $1.8 million and $2.3 million,
respectively. These assumptions are subject to the risk of change, including macroeconomic conditions, as they require
significant judgment and have inherent uncertainties that management or its actuaries may not control or anticipate. A detailed
discussion of our defined benefit pension plan is contained in Note 15 to our financial statements set forth in Item 8 of this
Annual Report on Form 10-K.
Results of Operations
The following discussion summarizes the key factors our management believes are necessary for an understanding of
our consolidated financial statements.
Year Ended December 31,
2024
2023
(in thousands)
Revenues:
Collaborative arrangements revenue
$
351,410 $
442,735
Total revenues
351,410
442,735
Costs and expenses:
Research and development
111,421
116,085
Selling, general and administrative
144,272
158,314
Restructuring
2,593
18,317
Acquired in-process research and development
—
1,095,449
Total costs and expenses
258,286
1,388,165
Income (loss) from operations
93,124
(945,430)
Other income (expense):
Interest expense and other financing costs
(33,034)
(21,629)
Interest and investment income
4,468
18,971
Gain on derivatives
—
19
Other
640
—
Other income (expense), net
(27,926)
(2,639)
Income (loss) before income taxes
65,198
(948,069)
Income tax expense
(64,318)
(83,490)
Net income (loss)
880
(1,031,559)
Less: Net loss attributable to noncontrolling interests
—
(29,320)
Net income (loss) attributable to Ironwood Pharmaceuticals, Inc.
$
880
$
(1,002,239)
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Year Ended December 31, 2024 Compared to Year Ended December 31, 2023
Revenues
Year Ended
December 31,
Change
2024
2023
$
(in thousands)
Revenues:
Collaborative arrangements revenue
$
351,410
$
442,735
$
(91,325)
Total revenues
$
351,410
$
442,735
$
(91,325)
Collaborative arrangements revenue. The decrease in collaborative arrangements revenue of $91.3 million for the
year ended December 31, 2024 compared to the year ended December 31, 2023 was primarily related to a $90.1 million
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 government and contractual rebates), partially offset by increases from prescription demand.
Cost and Expenses
Year Ended
December 31,
Change
2024
2023
$
(in thousands)
Costs and expenses:
Research and development
$
111,421
$
116,085
$
(4,664)
Selling, general and administrative
144,272
158,314
(14,042)
Restructuring
2,593
18,317
(15,724)
Acquired in-process research and development
—
1,095,449
(1,095,449)
Total costs and expenses
$
258,286
$
1,388,165
$
(1,129,879)
Research and development. The decrease in research and development expenses of $4.7 million for the year ended
December 31, 2024 compared to the year ended December 31, 2023 was primarily related to $11.3 million of share-based
compensation expense and $3.5 million in related payroll taxes recognized in the second quarter of 2023 immediately after the
closing of the VectivBio Acquisition in connection with the vesting acceleration of outstanding stock options and RSUs under
VectivBio’s 2021 Equity Incentive Plan, a $6.0 million payment to COUR in the second quarter of 2023 related to CNP-104 in
connection with the amendment of the COUR Collaboration Agreement, a $4.8 million reduction to research and development
expense in connection with the settlement of a license-related contract liability, and a $2.5 million decrease in external
linaclotide costs, partially offset by a $15.9 million increase of apraglutide program costs, a $6.0 million increase in
compensation, benefits, and other employee-related expenses, and a $2.0 million increase related to an amendment of the
COUR Collaboration Agreement.
Selling, general and administrative. Selling, general and administrative expenses decreased $14.0 million for the year
ended December 31, 2024 compared to the year ended December 31, 2023, primarily due to $16.2 million of share-based
compensation and $3.0 million in related payroll taxes recognized in the second quarter of 2023 immediately after the closing
of the VectivBio Acquisition in connection with the vesting acceleration of outstanding stock options and RSUs under
VectivBio’s 2021 Equity Incentive Plan, and a $0.9 million decrease in compensation, benefits, and other employee-related
expenses, partially offset by a $8.0 million increase in professional services costs (including $4.5 million related to
commercial launch planning for apraglutide, if approved).
Restructuring expenses. Restructuring expenses were $2.6 million for the year ended December 31, 2024 related to
employee severance, benefits and related costs for the VectivBio Acquisition-related workforce reduction. Restructuring
expenses were $18.3 million for the year ended December 31, 2023 and were comprised of $3.4 million of employee
severance, benefits and related costs for the headquarters-based workforce reduction and $14.9 million of employee
severance, benefits and related costs for the VectivBio Acquisition-related workforce reduction.
Acquired In-Process Research & Development. We incurred approximately $1.1 billion of expense during the year
ended December 31, 2023 in connection with the VectivBio Acquisition to acquire apraglutide.
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Other Income (Expense), Net
Year Ended
December 31,
Change
2024
2023
$
(in thousands)
Other income (expense):
Interest expense and other financing costs
$
(33,034)
$
(21,629)
$ (11,405)
Interest and investment income
4,468
18,971
(14,503)
Gain on derivatives
—
19
(19)
Other
640
—
640
Total other income (expense), net
$
(27,926)
$
(2,639)
$ (25,287)
Interest expense and other financing costs. Interest expense increased by $11.4 million during the year ended
December 31, 2024 compared to the year ended December 31, 2023 primarily due to $13.2 million of interest expense
incurred under the Revolving Credit Facility used to partially finance the VectivBio Acquisition in June 2023, partially offset
by a decrease of $1.3 million of interest expense incurred on the 2024 Convertible Notes.
Interest and investment income. Interest and investment income decreased by $14.5 million in the year ended
December 31, 2024 compared to the year ended December 31, 2023, primarily from a decrease in cash and investment
balances following the VectivBio Acquisition in June 2023.
Gain on derivatives. During the year ended December 31, 2023, we recorded an insignificant gain on derivatives
resulting from a decrease in the fair value of the Note Hedge Warrants, which terminated unexercised upon expiry in April
2023.
Other. During the year ended December 31, 2024, we recorded a gain of $0.6 million for pension-related activities.
Income taxes. During the year ended December 31, 2024, we recorded income tax expense of $64.3 million,
comprised of non-cash tax expense of $57.8 million and cash tax expense of $6.5 million for state income taxes in certain
states in which state taxable income exceeded available net operating losses. During the year ended December 31, 2023, we
recorded income tax expense of $83.5 million, comprised of non-cash tax expense of $74.1 million and cash tax expense of
$9.4 million for state income taxes in certain states in which state taxable income exceeded available net operating losses.
Liquidity and Capital Resources
As of December 31, 2024, we had $88.6 million of cash and cash equivalents. Our cash equivalents include amounts
held in money market funds, U.S. Treasury securities and commercial paper. We invest cash in excess of immediate
requirements in accordance with our investment policy, which limits the amounts we may invest in certain types of
investments and requires all investments held by us to be at least A- rated, with a remaining final maturity when purchased of
less than twenty-four months, so as to primarily achieve liquidity and capital preservation objectives.
We anticipate our cash balance and our expected net cash inflows from operations to allow us to meet our near-term
and long-term cash obligations, which are reflected in our consolidated balance sheets. Our most significant fixed obligations
are debt obligations and lease commitments, for which annual payments are disclosed in Note 10, Debt, and Note 7, Leases,
respectively, to our financial statements included elsewhere in this Annual Report on Form 10-K.
We may from time to time seek to retire, redeem or repurchase all or part of our outstanding debt through cash
purchases and/or exchanges, in open market purchases, privately negotiated transactions, by tender offer or otherwise. Such
repurchases, redemptions or exchanges, if any, of our debt will depend on prevailing market conditions, liquidity
requirements, contractual restrictions and other factors, and the amounts involved may be material.
In May 2021, our board of directors authorized a program to repurchase up to $150.0 million of our Class A Common
Stock. The program was completed in May 2022 and the repurchased shares were retired. Additional information regarding
the repurchase program is disclosed in Note 12, Stockholders’ Equity, to our financial statements included elsewhere in this
Annual Report on Form 10-K.
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Sources of Liquidity
We have financed our operations to date primarily through both the private sale of our preferred stock and the public
sale of our common stock, debt financings, and cash generated from our operations. As of December 31, 2024, our debt is
comprised of $200.0 million aggregate principal amount of convertible notes, due in 2026, and $385.0 million aggregate
principal amount outstanding under our Revolving Credit Facility, which we entered into in May 2023 to partially finance the
VectivBio Acquisition. The Revolving Credit Facility provides for $550.0 million of borrowing capacity and includes a $10.0
million letter of credit subfacility. Refer to Note 10, Debt, to our consolidated financial statements included elsewhere in this
Annual Report on Form 10-K, for information related to our debt obligations.
Summary of Cash Flows
The following table summarizes cash flows from operating, investing, and financing activities for the years ended
December 31, 2024, 2023, and 2022:
Year Ended December 31,
2024
2023
(in thousands)
Net cash provided by (used in):
Operating activities
$
103,549
$
183,427
Investing activities
(142)
(1,026,318)
Financing activities
(106,970)
277,160
Effect of exchange rate changes on cash, cash equivalents and restricted cash
(32)
(53)
Net increase (decrease) in cash, cash equivalents and restricted cash
$
(3,595)
$
(565,784)
Cash Flows from Operating Activities
Net cash provided by operating activities is derived by adjusting net income (loss) for non-cash items and changes in
operating assets and liabilities, which reflect timing differences between the receipt and payment of cash associated with
transactions and when they are recognized in the results of operations.
Net cash inflows during the year ended December 31, 2024 totaled $103.5 million and were derived primarily from
collaboration arrangements revenue related to sales of LINZESS in the U.S., partially offset by research and development
expenditures for apraglutide.
Net cash inflows during the year ended December 31, 2023 totaled $183.4 million and were derived primarily from
collaboration arrangements revenue related to sales of LINZESS in the U.S., partially offset by research and development
expenditures for apraglutide and acquisition-related costs in connection with the VectivBio Acquisition.
Cash Flows from Investing Activities
Cash used in investing activities for the year ended December 31, 2024 was insignificant and pertained to the
purchase of property and equipment.
Cash used in investing activities for the year ended December 31, 2023 totaled approximately $1.0 billion and
pertained primarily to the VectivBio Acquisition.
Cash Flows from Financing Activities
Cash used in financing activities for the year ended December 31, 2024 totaled $107.0 million was comprised
primarily of the repayment of $200.0 million aggregate principal on the 2024 Convertible Notes upon their maturity in June
2024, partially offset by $85.0 million of net borrowings under the Revolving Credit Facility and $11.0 million from stock
option exercises and employee stock purchases.
Cash provided by financing activities for the year ended December 31, 2023 totaled $277.2 million and was
generated primarily from the incurrence of $400.0 million of borrowings under the Revolving Credit Facility, net of
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$100.0 million of principal repayments. Additionally, we paid $26.3 million to acquire subsidiary shares from noncontrolling
interests to complete the squeeze-out merger in connection with the VectivBio Acquisition.
Funding Requirements
We began commercializing LINZESS in the U.S. with our collaboration partner, AbbVie, in the fourth quarter of
2012, and we currently derive a significant portion of our revenue from this collaboration. Our goal is to generate and
maintain positive cash flows, driven by increased revenue generated through sales of LINZESS and other commercial
activities and financial discipline, while continuing to invest in the development and commercialization of linaclotide,
apraglutide, and other product candidates.
Under our collaboration with AbbVie for North America, total net sales of LINZESS in the U.S., as recorded by
AbbVie, are reduced by commercial costs incurred by each party, and the resulting amount is shared equally between us and
AbbVie. Additionally, we receive royalties from AbbVie based on sales of linaclotide in its licensed territories outside of the
U.S. We believe revenues from our LINZESS partnership for the U.S. with AbbVie will continue to constitute a significant
portion of our total revenue for the foreseeable future and we cannot be certain that such revenues, as well as the revenues
from our other commercial activities, will continue to enable us to generate positive cash flows, or to do so in the timeframes
we expect. We also anticipate that we will continue to incur substantial expenses for the next several years as we further
develop and commercialize linaclotide in the U.S., develop and commercialize other product candidates, including
apraglutide, and invest in building our pipeline through internal or external opportunities. We believe that our cash on hand as
of December 31, 2024 will be sufficient to meet our projected operating needs at least through the next twelve months from
the issuance of these financial statements.
Our forecast of the period of time through which our financial resources will be adequate to support our operations,
including the underlying revenue expectations and estimates regarding the costs to continue to develop, obtain regulatory
approval for, and commercialize linaclotide in the U.S., develop and commercialize other product candidates, including
apraglutide, and our goal to generate and maintain positive cash flows, are forward-looking statements that involve risks and
uncertainties. Our actual results could vary materially and negatively from these and other forward-looking statements as a
result of a number of factors, including the factors discussed in the “Risk Factors” section of this Annual Report on Form 10-
K. We have based our estimates on assumptions that may prove to be wrong, and we could utilize our available capital
resources sooner than we currently expect.
Due to the numerous risks and uncertainties associated with the development and commercialization of our product
candidates, we are unable to estimate precisely the amounts of capital outlays and operating expenditures necessary to
develop, obtain regulatory approval for, and commercialize linaclotide, apraglutide and our other product candidates, in each
case, for all of the markets, indications, populations and formulations for which we believe each is suited. Our funding
requirements will depend on many factors, including, but not limited to, the following:
●
the revenue generated by sales of LINZESS and CONSTELLA and from any other sources;
●
the rate of progress and cost of our commercialization activities, including the expense we incur in marketing
and selling LINZESS in the U.S. and from any other sources;
●
the success of our third-party manufacturing activities;
●
the time and costs involved in developing, and obtaining regulatory approvals for, our product candidates,
including apraglutide, as well as the timing and cost of any post-approval development and regulatory
requirements;
●
the time and costs associated with commercial manufacturing, sales, marketing and distribution of apraglutide, if
approved;
●
the success of our research and development efforts;
●
the emergence of competing or complementary products;
●
the costs of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights;
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●
the terms and timing of any collaborative, licensing or other arrangements that we may establish, including
milestones, royalties or other payments due or payable under such agreements;
●
the settlement method used for our outstanding convertible notes; and
●
the acquisition of businesses, products and technologies and the impact of other strategic transactions, as well as
the cost and timing of evaluating, acquiring, and, if completed, integrating into our business operations any such
assets.
Financing Strategy
We may, from time to time, consider additional funding through a combination of new collaborative arrangements,
strategic alliances, and additional equity and debt financings or from other sources. We will continue to manage our capital
structure and to consider all financing opportunities, whenever they may occur, that could strengthen our long-term liquidity
profile. Any such capital transactions may or may not be similar to transactions in which we have engaged in the past. There
can be no assurance that any such financing opportunities will also be available on acceptable terms, if at all.
Off-Balance Sheet Arrangements
We do not have any relationships with unconsolidated entities or financial partnerships, such as entities often referred
to as structured finance or special purpose entities, that would have been established for the purpose of facilitating off-balance
sheet arrangements or other contractually narrow or limited purposes. As such, we are not exposed to any financing, liquidity,
market or credit risk that could arise if we had engaged in those types of relationships. We enter into guarantees in the ordinary
course of business related to the guarantee of our own performance and the performance of our subsidiaries.
New Accounting Pronouncements
For a discussion of recent accounting pronouncements, refer to Note 2, Summary of Significant Accounting Policies,
to our consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K. We did not otherwise adopt
any new accounting pronouncements during the fiscal year ended December 31, 2024 that had a material effect on our
consolidated financial statements included in this report.
Item 7A. Quantitative and Qualitative Disclosures about Market Risk
Interest Rate Risk
We are exposed to market risk related to changes in interest rates. We invest our cash in a variety of financial
instruments, principally securities issued by the U.S. government and its agencies, including collateralized reverse repurchase
agreements, and money market instruments, as well as commercial paper. The goals of our investment policy are preservation
of capital, fulfillment of liquidity needs and fiduciary control of cash and investments. We also seek to maximize income from
our investments without assuming significant risk.
Our primary exposure to market risk is interest income sensitivity, which is affected by changes in the general level
of interest rates, particularly because our investments are in short-term marketable securities. Due to the primarily short-term
duration of our investment portfolio and the low risk profile of our investments, an immediate 1% change in interest rates
would not have a material effect on the fair market value of our portfolio. Accordingly, we would not expect our operating
results or cash flows to be affected to any significant degree by the effect of a sudden change in market interest rates on our
investment portfolio.
We do not believe our cash and cash equivalents have significant risk of default or illiquidity. While we believe our
cash and cash equivalents do not contain excessive risk, we cannot provide absolute assurance that in the future our
investments will not be subject to adverse changes in market value. In addition, we maintain significant amounts of cash and
cash equivalents at one or more financial institutions that are in excess of federally insured limits. Given the
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potential instability of financial institutions, we cannot provide assurance that we will not experience losses on these deposits.
Our convertible senior notes bear interest at a fixed rate and therefore have minimal exposure to changes in interest
rates; however, because these interest rates are fixed, we may be paying a higher interest rate, relative to market, in the future
if our credit rating improves or other circumstances change.
We are exposed to market risks related to fluctuations in interest rates relating to our secured $550.0 million
Revolving Credit Facility. The increase or decrease in annual interest expense resulting from a 10% increase or decrease in the
applicable interest rate is $2.8 million.
Equity Price Risk
Our convertible senior notes include conversion and settlement provisions that are based on the price of our Class A
Common Stock at conversion or maturity of the notes. The amount of cash we may be required to pay is determined by the
price of our Class A Common Stock. The fair value of our convertible senior notes is dependent on the price and volatility of
our Class A Common Stock and will generally increase or decrease as the market price of our common stock changes.
To minimize the impact of potential dilution to our common stock upon conversion of the notes, we entered into the
Capped Calls with respect to the 2026 Convertible Notes.
The convertible senior notes and Capped Calls are more fully described in Note 10, Debt, in the accompanying notes
to our consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K.
Foreign Currency Risk
We are also exposed to risks related to changes in foreign currency exchange rates relating to our foreign operations.
The functional currency of our international subsidiaries is the local currency. We are exposed to foreign currency risk to the
extent that we enter into transactions denominated in currencies other than our subsidiaries’ respective functional currencies.
We are also exposed to unfavorable fluctuations of the U.S. dollar, which is our reporting currency, against the currencies of
our operating subsidiaries when their respective financial statements are translated into U.S. dollars for inclusion in our
consolidated financial statements. We do not currently hedge our foreign currency exchange rate risk. Foreign currency has
not had, nor do we believe that a decrease or increase in any foreign currency exchange rates would have, a material impact on
our results of operations.
Item 8. Financial Statements and Supplementary Data
Our consolidated financial statements, together with the independent registered public accounting firm, Ernst &
Young LLP (PCAOB ID: 42), report thereon, appear at pages F-1 through F-47, of this Annual Report on Form 10-K.
Item 9. Changes in and Disagreements With Accountants on Accounting and Financial Disclosure
None.
Item 9A. Controls and Procedures
Limitations on Effectiveness of Controls and Procedures
In designing and evaluating our disclosure controls and procedures, management recognizes that any controls and
procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving the desired control
objectives. In addition, the design of disclosure controls and procedures must reflect the fact that there are resource constraints
and that management is required to apply judgment in evaluating the benefits of possible controls and procedures relative to
their costs.
Evaluation of Disclosure Controls and Procedures
As required by Rule 13a-15(b) of the Securities Exchange Act of 1934, or Exchange Act, our management, including
our principal executive officer and our principal financial officer, conducted an evaluation as of the end of the
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period covered by this Annual Report on Form 10-K of the effectiveness of the design and operation of our disclosure controls
and procedures. Based on that evaluation, our principal executive officer and principal financial officer concluded that, as a
result of material weaknesses in internal control over financial reporting as described below, our disclosure controls and
procedures were not effective at the reasonable assurance level in ensuring that information required to be disclosed by us in
the reports that we file or submit under the Exchange Act is recorded, processed, summarized and reported within the time
periods specified in the SEC’s rules and forms. Disclosure controls and procedures include, without limitation, controls and
procedures designed to ensure that information required to be disclosed by us in the reports we file under the Exchange Act is
accumulated and communicated to our management, including our principal executive officer and principal financial officer,
as appropriate to allow timely decisions regarding required disclosure.
Management’s Report on Internal Control Over Financial Reporting
Our management is responsible for establishing and maintaining adequate internal control over our financial
reporting. Internal control over financial reporting is defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act as the
process designed by, or under the supervision of, our Chief Executive Officer and Chief Financial Officer, and effected by our
board of directors, management and other personnel, to provide reasonable assurance regarding the reliability of our financial
reporting and the preparation of our financial statements for external purposes in accordance with generally accepted
accounting principles, and includes those policies and procedures that:
(1)
pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions
and dispositions of assets;
(2)
provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial
statements in accordance with generally accepted accounting principles, and that receipts and expenditures
are being made only in accordance with the authorizations of management and directors; and
(3)
provide reasonable assurance regarding the prevention or timely detection of unauthorized acquisition, use
or disposition of assets that could have a material effect on our financial statements.
Under the supervision and with the participation of our management, including our Chief Executive Officer and
Chief Financial Officer, we conducted an evaluation of the effectiveness of our internal control over financial reporting based
on the framework provided in Internal Control—Integrated Framework issued by the Committee of Sponsoring Organizations
of the Treadway Commission (2013 framework). Based on this evaluation, our management concluded that our internal
control over financial reporting was not effective at the reasonable assurance level as of December 31, 2024 as a result of
material weaknesses in internal control over financial reporting as described below.
We identified certain control deficiencies in the design and implementation of our internal control over financial
reporting that constituted material weaknesses. A material weakness is a deficiency, or a combination of deficiencies, in
internal control over financial reporting, such that there is a reasonable possibility that a material misstatement of the
Company’s annual or interim financial statements will not be prevented or detected on a timely basis. Specifically, we did not
design and or implement an effective control environment or control activities as further detailed below.
●
We did not have appropriately designed entity-level controls impacting the (1) control environment, (2) risk
assessment procedures, (3) identification of control activities, (4) information and communication and (5)
monitoring activities to prevent or detect material misstatements to the financial statements and assess whether the
components of internal control were present and functioning. We did not adequately communicate to employees
responsible for the execution of controls the relevant information, including objectives and responsibilities,
necessary to support the functioning of internal controls over financial reporting. We did not develop and perform
sufficient ongoing evaluations to ascertain whether the components of internal control were present and functioning
or perform adequate risk assessment procedures within our control environment. These deficiencies were attributed
to an insufficient number of qualified resources to effectively perform control design and execution activities and
oversee internal control over financial reporting.
●
We did not design and maintain effective information technology (IT) general controls around our key accounting
and reporting IT systems, specifically related to change management, user access, and data
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migration, as part of the Company’s enterprise resource planning (ERP) system, and these controls were not
operating effectively. Consequently, IT application controls (ITAC) and IT dependent manual (ITDM) business
process controls that rely upon information from the ERP system, were also deemed ineffective.
●
We did not design and/or operate effective controls over the financial statement close process as well as transaction
level controls across various significant accounts and processes to address all material risk of misstatement as of
December 31, 2024. Controls were not designed or operating effectively to support (1) the sufficiency of the review
including level of precision and retention of evidence, (2) the completeness and accuracy of key data and reports
used in the control activities, and/or (3) the timeliness of execution of management controls.
●
We did not design and/or operate effective ITDM and ITAC business process controls including appropriate
segregation of duties and the completeness and accuracy of data and reports used in control activities and timeliness
of execution to address the risk related to the initiation, authorization, and recording of expenditures.
Notwithstanding the material weaknesses, no material misstatements were identified in our financial statements as of
and for the year ended December 31, 2024 and we have concluded that the financial statements and other financial
information included in this Annual Report fairly present in all material respects our financial condition, results of operations
and cash flows for the periods presented in conformity with accounting principles generally accepted in the United States.
The Company’s independent registered public accounting firm, Ernst & Young LLP, has audited the effectiveness of
the Company’s internal control over financial reporting as of December 31, 2024. Their report is set forth herein.
Remediation of Material Weaknesses in Internal Control over Financial Reporting
Immediately following the identification of the material weaknesses described above, and with the oversight of the
Audit Committee, we commenced a process to remediate the underlying control deficiencies contributing to the above
material weaknesses. We have started remediating the control deficiencies and will continue these efforts throughout 2025.
Our plan for remediation includes the following:
●
We have started the process of identifying and recruiting additional personnel who have experience working at
public companies and expertise in accounting, financial reporting and internal controls commensurate with the type,
volume and complexity of our operations. We have also commenced the search for a Head of IT and plan to
centralize the accounting for foreign subsidiaries by transitioning the majority of accounting operations to the U.S. in
2025;
●
We have implemented incremental system approvals and manual monitoring controls to mitigate segregation of
duties risk within certain financial processes, and will continue to engage with third party consultants with the
requisite knowledge and experience to assess our ERP system and identify opportunities to enhance our use of the
system while maintaining appropriate levels of segregation of duties;
●
We will enhance our system implementation and development lifecycle documentation to include the following:
o
Formally define policies and procedures for user roles, including emergency access roles, and requirements
for lookback reviews during the implementation and post-implementation user access review phases;
o
The nature and level of change management documentation required to be maintained during the
implementation and post-implementation review phases; and
o
Enhance policies and procedures around data migration, including formally defining the specific material
data elements for validation; the procedures to be followed when validating the completeness and accuracy
of data migrations; and the level of documentation required to evidence that data migration testing was
performed and reviewed;
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●
We will enhance our training processes, which include conducting and delivering training on a regular basis to our
finance and accounting and IT team members on how to execute internal control responsibilities, including the
importance of completeness and accuracy procedures and maintaining sufficient documentation and/or evidence to
support the performance of control activities; and
●
To the extent certain control improvements were implemented in 2024 that management believes are operating, but
did not have the requisite time period to demonstrate operating effectiveness as of December 31, 2024, we will
continue to focus on effectively operating such controls.
When fully implemented and operational, we believe the measures described above will remediate the material
weaknesses we have identified and strengthen our internal control over financial reporting. As we continue to evaluate and
work to improve our internal control over financial reporting, our management may determine to take additional measures.
The measures we are implementing are subject to continued management review supported by confirmation and
testing, as well as Audit Committee oversight. Management and the Audit Committee remain committed to the
implementation of remediation efforts to address the material weaknesses. We will continue to implement measures to remedy
our internal control deficiencies, though there can be no assurance that our efforts will be successful or avoid potential future
material weaknesses. In addition, until remediation steps have been completed and are operated for a sufficient period of time,
and subsequent evaluation of their effectiveness is completed, the material weaknesses previously disclosed, and as described
above, will continue to exist.
Changes in Internal Control Over Financial Reporting
As required by Rule 13a-15(d) of the Exchange Act, our management, including our principal executive officer and
our principal financial officer, conducted an evaluation of the internal control over financial reporting to determine whether
any changes occurred during the quarter ended December 31, 2024 that have materially affected, or are reasonably likely to
materially affect, our internal controls over financial reporting.
Based on management’s evaluation, and except as described above, our principal executive officer and principal
financial officer concluded that no other changes during the quarter ended December 31, 2024 materially affected, or were
reasonably likely to materially affect, our internal control over financial reporting.
During the third quarter of 2024, we implemented a new global enterprise resource planning, or ERP system. The
implementation of the system will continue through early 2025. The ERP system replaces the existing financial systems we
have historically relied on. Throughout the implementation, we reassessed our processes and procedures, which resulted in
changes to our internal control over financial reporting. In connection with this implementation, we identified a material
weakness in our information technology general controls, as described above.
On June 29, 2023, we acquired VectivBio and in our 2023 Annual Report on Form 10-K, we excluded VectivBio
from our evaluation of internal control over financial reporting. This exclusion was in accordance with the SEC’s guidance
that a recently acquired business may be omitted from the assessment scope for up to one year from the date of acquisition.
We have extended our oversight and monitoring processes that support our internal control over financial reporting, as well as
our disclosure controls and procedures, to the acquired operations of VectivBio, and we have incorporated VectivBio into our
annual assessment of internal control over financial reporting for our fiscal year ended December 31, 2024.
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Report of Independent Registered Public Accounting Firm
To the Stockholders and the Board of Directors of Ironwood Pharmaceuticals, Inc.
Opinion on Internal Control Over Financial Reporting
We have audited Ironwood Pharmaceuticals, Inc.’s internal control over financial reporting as of December 31, 2024, based on
criteria established in Internal Control—Integrated Framework issued by the Committee of Sponsoring Organizations of the
Treadway Commission (2013 framework) (the COSO criteria). In our opinion, because of the effect of the material
weaknesses described below on the achievement of the objectives of the control criteria, Ironwood Pharmaceuticals, Inc. (the
Company) has not maintained effective internal control over financial reporting as of December 31, 2024, based on the COSO
criteria.
A material weakness is a deficiency, or combination of deficiencies, in internal control over financial reporting, such that there
is a reasonable possibility that a material misstatement of the company’s annual or interim financial statements will not be
prevented or detected on a timely basis. The following material weaknesses have been identified and included in
management’s assessment. Management has identified pervasive material weaknesses throughout the Company’s internal
control processes that involve the control environment, risk assessment, control activity, information and communication, and
monitoring components of the COSO framework, as well as internal controls across various significant accounts and
information technology general controls, that are described in more detail in management’s assessment.
We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States)
(PCAOB), the 2024 consolidated financial statements of the Company. These material weaknesses were considered in
determining the nature, timing and extent of audit tests applied in our audit of the 2024 consolidated financial statements, and
this report does not affect our report dated March 31, 2025, which expressed an unqualified opinion thereon.
Basis for Opinion
The Company’s management is responsible for maintaining effective internal control over financial reporting and for its
assessment of the effectiveness of internal control over financial reporting included in the accompanying Management’s
Report on Internal Control Over Financial Reporting. Our responsibility is to express an opinion on the Company’s internal
control over financial reporting based on our audit. We are a public accounting firm registered with the PCAOB and are
required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable
rules and regulations of the Securities and Exchange Commission and the PCAOB.
We conducted our audit in accordance with the standards of the PCAOB. Those standards require that we plan and perform the
audit to obtain reasonable assurance about whether effective internal control over financial reporting was maintained in all
material respects.
Our audit included obtaining an understanding of internal control over financial reporting, assessing the risk that a material
weakness exists, testing and evaluating the design and operating effectiveness of internal control based on the assessed risk,
and performing such other procedures as we considered necessary in the circumstances. We believe that our audit provides a
reasonable basis for our opinion.
Definition and Limitations of Internal Control Over Financial Reporting
A company’s internal control over financial reporting is a process designed to provide reasonable assurance regarding the
reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally
accepted accounting principles. A company’s internal control over financial reporting includes those policies and procedures
that (1) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and
dispositions of the assets of the company; (2) provide reasonable assurance that transactions are recorded as necessary to
permit preparation of financial statements in accordance with generally accepted accounting principles, and that receipts and
expenditures of the company are being made only in accordance with authorizations of
Table of Contents
86
management and directors of the company; and (3) provide reasonable assurance regarding prevention or timely detection of
unauthorized acquisition, use, or disposition of the company’s assets that could have a material effect on the financial
statements.
Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also,
projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate
because of changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate.
/s/ Ernst & Young LLP
Boston, Massachusetts
March 31, 2025
Table of Contents
87
Item 9B. Other Information
(a) On February 27, 2025, we issued a press release announcing unaudited financial results for the quarter and year
ended December 31, 2024, which was furnished on a Current Report on Form 8-K filed on February 27, 2025, and we
presented, via webcast, a supplemental earnings presentation setting forth such results, or collectively, the Earnings Materials.
Subsequent to the date of presenting our Earnings Materials, we recorded immaterial adjustments to the fourth quarter and full
year of 2024 results. We have updated the Earnings Materials on the Investors section of our website at
www.ironwoodpharma.com to reflect the adjustments made.
(b) During the quarter ended December 31, 2024, no director or officer (as defined in Rule 16a-1(f) under the
Exchange Act) of the Company adopted or terminated a “Rule 10b5-1 trading arrangement” or “non-Rule 10b5-1 trading
arrangement,” as each term is defined in Item 408(a) of Regulation S-K.
Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections
Not applicable.
PART III
Item 10. Directors, Executive Officers and Corporate Governance
We have adopted a code of business conduct and ethics applicable to our directors, officers, employees, consultants
and all their immediate family or other household members. A copy of that code is available on our corporate website at
http://www.ironwoodpharma.com. Any amendments to the code of business conduct and ethics, and any waivers thereto that
are required to be disclosed pursuant to SEC rules, will be also available on our corporate website. A printed copy of these
documents will be made available upon request. The content on our website is not incorporated by reference into this Annual
Report on Form 10-K.
We have adopted an insider trading prevention policy governing the purchase, sale and other dispositions of our
securities that applies to each of our directors, officers, employees, consultants and their immediate family members. We
believe the insider trading prevention policy is reasonably designed to promote compliance with insider trading laws, rules
and regulations, and Nasdaq listing standards. A copy of our insider trading prevention policy is filed as Exhibit 19.1 to this
Annual Report on Form 10-K. It is also our policy that we do not engage in transactions in Company securities while in
possession of material nonpublic information concerning the Company or our securities.
The other information required by this item is incorporated by reference from our proxy statement for our 2025
Annual Meeting of Stockholders.
Item 11. Executive Compensation
The information required by this item is incorporated by reference from our proxy statement for our 2025 Annual
Meeting of Stockholders.
Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters
The information relating to security ownership of certain beneficial owners of our common stock and information
relating to the security ownership of our management required by this item is incorporated by reference from our proxy
statement for our 2025 Annual Meeting of Stockholders.
The table below sets forth information with regard to securities authorized for issuance under our equity
compensation plans as of December 31, 2024. As of December 31, 2024, we had four active equity compensation plans, each
of which was approved by our stockholders:
●
Amended and Restated 2010 Employee, Director and Consultant Equity Incentive Plan;
●
2019 Equity Incentive Plan;
●
Amended and Restated 2019 Equity Incentive Plan; and
Table of Contents
88
●
Amended and Restated 2010 Employee Stock Purchase Plan.
Plan Category
Number of securities
to be issued upon
exercise of
outstanding options,
warrants and rights
(1)
Weighted-
average
exercise
price of
outstanding
options,
warrants,
and rights
(2)
Number of securities
remaining available
for future issuance
under equity
compensation plans
(excluding securities
reflected in column
(a)) (3)
(a)
(b)
(c)
Equity compensation plans approved by security holders
11,094,274
$12.37
12,474,318
Equity compensation plans not approved by security holders
—
—
—
Total
11,094,274
$12.37
12,474,318
(1) Amount includes the number of shares subject to issuance upon exercise of 4,540,264 outstanding stock options and
vesting of 6,554,010 restricted stock units.
(2) Amount includes all outstanding stock options but does not include restricted stock units, which do not have an exercise
price.
(3) Consists of 8,391,775 shares available for future issuance under the Amended and Restated 2019 Equity Incentive Plan
and 4,082,543 shares available for future issuance under the Amended and Restated 2010 Employee Stock Purchase Plan.
Item 13. Certain Relationships and Related Transactions, and Director Independence
The information required by this item is incorporated by reference from our proxy statement for our 2025 Annual
Meeting of Stockholders.
Item 14. Principal Accountant Fees and Services
The information required by this item is incorporated by reference from our proxy statement for our 2025 Annual
Meeting of Stockholders.
Table of Contents
89
PART IV
Item 15. Exhibits and Financial Statement Schedules
1.
List of documents filed as part of this report
1.
Consolidated Financial Statements listed under Part II, Item 8 and included herein by reference.
2.
Consolidated Financial Statement Schedules
No schedules are submitted because they are not applicable, not required or because the information is included in
the Consolidated Financial Statements or Notes to Consolidated Financial Statements.
3.
Exhibits
Incorporated by reference herein
Number
Description
Form
Date
2.1
Separation Agreement, dated as of March
30, 2019, by and between Ironwood
Pharmaceuticals, Inc. and Cyclerion
Therapeutics, Inc.
Current Report on Form 8-K (File
No. 001-34620)
April 4, 2019
2.2
Transaction Agreement, dated May 21,
2023, by and between Ironwood
Pharmaceuticals, Inc. and VectivBio
Holding AG
Current Report on Form 8-K (File
No. 001-34620)
May 22, 2023
3.1
Eleventh Amended and Restated Certificate
of Incorporation
Annual Report on Form 10-K (File
No. 001-34620)
March 30, 2010
3.2
Certificate of Retirement
Registration Statement on Form 8-
A/A (File No. 001-34620)
January 3, 2019
3.3
Certificate of Amendment
Current Report on Form 8-K (File
No. 001-34620)
May 31, 2019
3.4
Fifth Amended and Restated Bylaws
Annual Report on Form 10-K (File
No. 001-34620)
March 30, 2010
4.1
Specimen Class A Common Stock
certificate
Registration Statement on Form S-
1, as amended (File No. 333-
163275)
January 20, 2010
4.2
Indenture, dated as of August 12, 2019, by
and between Ironwood Pharmaceuticals,
Inc. and U.S. Bank National Association
(including the form of the 1.50%
Convertible Senior Note due 2026)
Current Report on Form 8-K (File
No. 001-34620)
August 13, 2019
4.2.1
Form of 1.50% Convertible Senior Note due
2026
Current Report on Form 8-K (File
No. 001-34620)
August 13, 2019
4.3
Description of Securities of Ironwood
Pharmaceuticals, Inc.
Annual Report on Form 10-K (File
No. 001-34620)
February 17, 2021
Table of Contents
90
10.1#
Amended and Restated 2010 Employee,
Director and Consultant Equity Incentive
Plan
Registration Statement on Form S-
8, as amended (File No. 333-
184396)
October 12, 2012
10.1.1#
Form of Stock Option Agreement under the
Amended and Restated 2010 Employee,
Director and Consultant Equity Incentive
Plan
Quarterly Report on Form 10-Q
(File No. 001-34620)
November 6, 2018
10.1.2#
Form of Restricted Stock Unit Agreement
under the Amended and Restated 2010
Employee, Director and Consultant Equity
Incentive Plan
Quarterly Report on Form 10-Q
(File No. 001-34620)
November 6, 2018
10.2#
2019 Equity Incentive Plan
Quarterly Report on Form 10-Q
(File No. 001-34620)
July 30, 2019
10.2.1#
Form of Non-statutory Stock Option
Agreement under the 2019 Equity Incentive
Plan
Quarterly Report on Form 10-Q
(File No. 001-34620)
July 30, 2019
10.2.2#
Form of Restricted Stock Unit Agreement
under the 2019 Equity Incentive Plan
Quarterly Report on Form 10-Q
(File No. 001-34620)
July 30, 2019
10.2.3#
Form of Restricted Stock Agreement under
the 2019 Equity Incentive Plan
Quarterly Report on Form 10-Q
(File No. 001-34620)
July 30, 2019
10.2.4#
Form of Performance-Based Restricted
Stock Unit Award Agreement under the
2019 Equity Incentive Plan
Quarterly Report on Form 10-Q
(File No. 001-34620)
May 6, 2020
10.3#
Amended and Restated 2019 Equity
Incentive Plan
Current Report on Form 8-K (File
No. 001-34620)
June 22, 2023
10.3.1#
Form of Restricted Stock Unit Agreement
under the Amended and Restated 2019
Equity Incentive Plan
Quarterly Report on Form 10-Q
(File No. 001-34620)
November 9, 2023
10.4#
Amended and Restated 2010 Employee
Stock Purchase Plan
Annual Report on Form 10-K (File
No. 001-34620)
February 13, 2020
10.5#
Change of Control Severance Benefit Plan,
as amended and restated
Quarterly Report on Form 10-Q
(File No. 001-34620)
April 29, 2014
10.6#
Form of Executive Severance Agreement
Annual Report on Form 10-K (File
No. 001-34620)
February 25, 2019
10.7#
Form of Executive Severance Agreement
Current Report on Form 8-K (File
No. 001-34620)
December 1, 2021
10.8#
Second Amended and Restated Executive
Severance Agreement, dated as of June 22,
2021, between Ironwood Pharmaceuticals,
Inc. and Thomas McCourt
Current Report on Form 8-K/A
(File No. 001-34620)
June 24, 2021
Table of Contents
91
10.9#
Second Amended and Restated Non-
employee Director Compensation Policy,
effective January 1, 2024
Annual Report on Form 10-K (File
No. 001-34620)
February 16, 2024
10.10#
Form of Indemnification Agreement with
Directors and Officers
Registration Statement on Form S-
1, as amended (File No. 333-
163275)
December 23, 2009
10.11+
Collaboration Agreement, dated as of
September 12, 2007, as amended on
November 3, 2009, by and between Forest
Laboratories, Inc. and Ironwood
Pharmaceuticals, Inc.
Registration Statement on Form S-
1, as amended (File No. 333-
163275)
February 2, 2010
10.11.1
Amendment No. 2 to the Collaboration
Agreement, dated as of January 8, 2013, by
and between Forest Laboratories, Inc. and
Ironwood Pharmaceuticals, Inc.
Annual Report on Form 10-K (File
No. 001-34620)
February 21, 2013
10.12+
Commercial Agreement, dated as of January
31, 2017, by and among Allergan USA, Inc.,
Forest Laboratories, LLC and Ironwood
Pharmaceuticals, Inc.
Quarterly Report on Form 10-Q
(File No. 001-34620)
May 8, 2017
10.13+
License Agreement, dated as of April 30,
2009, by and between Allergan
Pharmaceuticals International Ltd. (formerly
with Almirall, S.A.) and Ironwood
Pharmaceuticals, Inc.
Registration Statement on Form S-
1, as amended (File No. 333-
163275)
February 2, 2010
10.13.1+
Amendment No. 1 to License Agreement,
dated as of June 11, 2013, by and between
Allergan Pharmaceuticals International Ltd.
(formerly with Almirall, S.A.) and Ironwood
Pharmaceuticals, Inc.
Quarterly Report on Form 10-Q
(File No. 001-34620)
August 8, 2013
10.13.2+
Amendment to the License Agreement,
dated as of October 26, 2015, by and
between Allergan Pharmaceuticals
International Ltd. and Ironwood
Pharmaceuticals, Inc.
Annual Report on Form 10-K (File
No. 001-34620)
February 19, 2016
10.13.3+
Amendment to the License Agreement dated
as of January 31, 2017, by and between
Allergan Pharmaceuticals International Ltd.,
and Ironwood Pharmaceuticals, Inc.
Quarterly Report on Form 10-Q
(File No. 001-34620)
May 8, 2017
10.14+
Novation Agreement, dated as of
October 26, 2015, by and among
Almirall, S.A., Allergan Pharmaceuticals
International Ltd. and Ironwood
Pharmaceuticals, Inc.
Annual Report on Form 10-K (File
No. 001-34620)
February 19, 2016
Table of Contents
92
10.15++
Amended and Restated License Agreement,
dated as of August 1, 2019, by and between
Ironwood Pharmaceuticals, Inc. and Astellas
Pharma Inc.
Current Report on Form 8-K (File
No. 001-34620
August 1, 2019
10.15.1
Amendment to the Amended and Restated
License Agreement, dated as of January 8,
2021, by and between Ironwood
Pharmaceuticals, Inc. and Astellas Pharma
Inc.
Annual Report on Form 10-K (File
No. 001-34620)
February 17, 2021
10.16++
Amended and Restated License and
Collaboration Agreement, dated as of
September 16, 2019, by and between
AstraZeneca AB and Ironwood
Pharmaceuticals, Inc.
Current Report on Form 8-K (File
No. 001-34620)
September 18, 2019
10.17+
Commercial Supply Agreement, dated as of
June 23, 2010, by and among PolyPeptide
Laboratories, Inc. and Polypeptide
Laboratories (SWEDEN) AB, Forest
Laboratories, Inc. and Ironwood
Pharmaceuticals, Inc.
Quarterly Report on Form 10-Q
(File No. 001-34620)
August 10, 2010
10.18+
Commercial Supply Agreement, dated as of
March 28, 2011, by and among Corden
Pharma Colorado, Inc. (f/k/a Roche
Colorado Corporation), Ironwood
Pharmaceuticals, Inc. and Forest
Laboratories, Inc.
Quarterly Report on Form 10-Q
(File No. 001-34620)
May 13, 2011
10.18.1+
Amendment No. 3 to Commercial Supply
Agreement, dated as of November 26, 2013,
by and between Corden Pharma
Colorado, Inc. (f/k/a Roche Colorado
Corporation), Ironwood
Pharmaceuticals, Inc. and Forest
Laboratories, Inc.
Annual Report on Form 10-K (File
No. 001-34620)
February 7, 2014
10.19++
Amended and Restated Exclusive License
Agreement by and between Ferring
International Center S.A. and GlyPharma
Therapeutic Inc. dated as of December 6,
2016, as amended
Registration Statement on Form F-1
(File No. 333-254523)
March 19, 2021
10.20++
Development and Commercialization
Agreement by and between VectivBio AG
and Asahi Kasei Pharma Corporation, dated
as of March 30, 2022
Annual Report on Form 20-F (File
No. 001-40316)
April 7, 2022
Table of Contents
93
10.21
Credit Agreement, dated May 21, 2023, by
and among Ironwood Pharmaceuticals, Inc.,
as borrower, Wells Fargo Bank, National
Association, as administrative agent,
collateral agent, a letter of credit issuer and
a lender, and the other agents, lenders and
letter of credit issuers parties thereto
Current Report on Form 8-K (File
No. 001-34620)
May 22, 2023
10.21.1
Amendment No. 1 to Credit Agreement,
dated September 27, 2024, by and among
Ironwood Pharmaceuticals, Inc., as
borrower, Wells Fargo Bank, National
Association, as administrative agent,
collateral agent, a letter of credit issuer and
a lender, and the other agents, lenders and
letter of credit issuers parties thereto
Current Report on Form 8-K (File
No. 001-34620)
September 30, 2024
10.22
Lease Agreement for facilities at 100
Summer Street, Boston, Massachusetts,
dated as of June 11, 2019, by and between
Ironwood Pharmaceuticals, Inc. and MA-
100 Summer Street Owner, L.L.C.
Current Report on Form 8-K (File
No. 001-34620)
June 13, 2019
10.23
Tax Matters Agreement, dated as of March
30, 2019, by and between Ironwood
Pharmaceuticals, Inc. and Cyclerion
Therapeutics, Inc.
Current Report on Form 8-K (File
No. 001-34620)
April 4, 2019
10.24
Employee Matters Agreement, dated as of
March 30, 2019, by and between Ironwood
Pharmaceuticals, Inc. and Cyclerion
Therapeutics, Inc.
Current Report on Form 8-K (File
No. 001-34620)
April 4, 2019
10.25
Base Call Option Transaction Confirmation
for the 2026 Notes, dated as of August 7,
2019, between Ironwood Pharmaceuticals,
Inc. and JPMorgan Chase Bank, National
Association
Current Report on Form 8-K (File
No. 001-34620)
August 13, 2019
10.26
Base Call Option Transaction Confirmation,
for the 2026 Notes, dated as of August 7,
2019, between Ironwood Pharmaceuticals,
Inc. and Credit Suisse Capital LLC
Current Report on Form 8-K (File
No. 001-34620)
August 13, 2019
10.27
Additional Call Option Transaction
Confirmation for the 2026 Notes, dated as
of August 12, 2019, between Ironwood
Pharmaceuticals, Inc. and JPMorgan Chase
Bank, National Association
Current Report on Form 8-K (File
No. 001-34620)
August 13, 2019
Table of Contents
94
10.28
Additional Call Option Transaction
Confirmation for the 2026 Notes, dated as
of August 12, 2019, between Ironwood
Pharmaceuticals, Inc. and Credit Suisse
Capital LLC
Current Report on Form 8-K (File
No. 001-34620)
August 13, 2019
19.1*
Insider Trading Prevention Policy
21.1*
Subsidiaries of Ironwood
Pharmaceuticals, Inc.
23.1*
Consent of Independent Registered Public
Accounting Firm
31.1*
Certification of Chief Executive Officer
pursuant to Rules 13a-14 or 15d-14 of the
Exchange Act
31.2*
Certification of Chief Financial Officer
pursuant to Rules 13a-14 or 15d-14 of the
Exchange Act
32.1‡
Certification of Chief Executive Officer
pursuant to Rules 13a-14(b) or 15d-14(b) of
the Exchange Act and 18 U.S.C.
Section 1350
32.2‡
Certification of Chief Financial Officer
pursuant to Rules 13a-14(b) or 15d-14(b) of
the Exchange Act and 18 U.S.C.
Section 1350
97.1
Policy for Recoupment of Incentive
Compensation
Annual Report on Form 10-K (File
No. 001-34620)
February 16, 2024
101.INS*
XBRL Instance Document – The Instance
Document does not appear in the Interactive
Data Files because its XBRL tags are
embedded within the Inline XBRL
document
101.SCH*
XBRL Taxonomy Extension Schema
Document
101.CAL*
XBRL Taxonomy Extension Calculation
Linkbase Document
101.LAB*
XBRL Taxonomy Extension Label Linkbase
Database
101.PRE*
XBRL Taxonomy Extension Presentation
Linkbase Document
101.DEF*
XBRL Taxonomy Extension Definition
Linkbase Document
Table of Contents
95
104*
The cover page from this Annual Report on
Form 10-K, formatted in Inline XBRL
*
Filed herewith.
‡
Furnished herewith.
+
Confidential treatment has been granted as to certain portions of the exhibit, which portions have been omitted and have
been separately filed with the SEC pursuant to the confidential treatment request.
++ Portions of this exhibit have been omitted pursuant to Item 601(b)(10)(iv) of Regulation S-K.
#
Management contract or compensatory plan, contract, or arrangement.
Item 16. Form 10-K Summary
None.
Table of Contents
96
SIGNATURES
Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the registrant has duly
caused this report to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of Boston,
Commonwealth of Massachusetts, on the 31st day of March 2025.
Ironwood Pharmaceuticals, Inc.
By:
/s/ Thomas McCourt
Thomas McCourt
Chief Executive Officer
Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, this report has been
signed below by the following persons on behalf of the registrant and in the capacities and on the date indicated.
Signature
Title
Date
/s/ Thomas McCourt
Chief Executive Officer and Director (Principal Executive
Officer)
March 31, 2025
Thomas McCourt
/s/ Gregory Martini
Senior Vice President, Chief Financial Officer (Principal
Financial Officer)
March 31, 2025
Gregory Martini
/s/ Ronald Silver
Senior Vice President, Corporate Controller (Principal
Accounting Officer)
March 31, 2025
Ronald Silver
/s/ Julie H. McHugh
Chair of the Board
March 31, 2025
Julie H. McHugh
/s/ Mark Currie
Director
March 31, 2025
Mark Currie
Director
Alexander Denner
/s/ Andrew Dreyfus
Director
March 31, 2025
Andrew Dreyfus
/s/ Jon Duane
Director
March 31, 2025
Jon Duane
/s/ Marla Kessler
Director
March 31, 2025
Marla Kessler
/s/ Catherine Moukheibir
Director
March 31, 2025
Catherine Moukheibir
/s/ Jay P. Shepard
Director
March 31, 2025
Jay P. Shepard
Table of Contents
F-1
Index to Consolidated Financial Statements of
Ironwood Pharmaceuticals, Inc.
Page
Report of Independent Registered Public Accounting Firm
F-2
Consolidated Balance Sheets as of December 31, 2024 and 2023
F-4
Consolidated Statements of Income (Loss) for the Years Ended December 31, 2024, 2023, and 2022
F-5
Consolidated Statements of Comprehensive Income (Loss) for the Years Ended December 31, 2024, 2023, and 2022
F-6
Consolidated Statements of Stockholders’ Equity (Deficit) for the Years Ended December 31, 2024, 2023, and 2022
F-7
Consolidated Statements of Cash Flows for the Years Ended December 31, 2024, 2023, and 2022
F-8
Notes to Consolidated Financial Statements
F-9
Table of Contents
F-2
Report of Independent Registered Public Accounting Firm
To the Stockholders and the Board of Directors of Ironwood Pharmaceuticals, Inc.
Opinion on the Financial Statements
We have audited the accompanying consolidated balance sheets of Ironwood Pharmaceuticals, Inc. (the Company) as of
December 31, 2024 and 2023, the related consolidated statements of income (loss), comprehensive income (loss),
stockholders' equity (deficit) and cash flows for each of the three years in the period ended December 31, 2024, and the related
notes (collectively referred to as the “consolidated financial statements”). In our opinion, the consolidated financial statements
present fairly, in all material respects, the financial position of the Company at December 31, 2024 and 2023, and the results
of its operations and its cash flows for each of the three years in the period ended December 31, 2024, in conformity with U.S.
generally accepted accounting principles.
We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States)
(PCAOB), the Company's internal control over financial reporting as of December 31, 2024, based on criteria established in
Internal Control—Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission
(2013 framework), and our report dated March 31, 2025 expressed an adverse opinion thereon.
Basis for Opinion
These financial statements are the responsibility of the Company's management. Our responsibility is to express an opinion on
the Company’s financial statements based on our audits. We are a public accounting firm registered with the PCAOB and are
required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable
rules and regulations of the Securities and Exchange Commission and the PCAOB.
We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform
the audit to obtain reasonable assurance about whether the financial statements are free of material misstatement, whether due
to error or fraud. Our audits included performing procedures to assess the risks of material misstatement of the financial
statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included
examining, on a test basis, evidence regarding the amounts and disclosures in the financial statements. Our audits also
included evaluating the accounting principles used and significant estimates made by management, as well as evaluating the
overall presentation of the financial statements. We believe that our audits provide a reasonable basis for our opinion.
Critical Audit Matter
The critical audit matter communicated below is a matter arising from the current period audit of the financial statements that
was communicated or required to be communicated to the audit committee and that: (1) relates to accounts or disclosures that
are material to the financial statements and (2) involved our especially challenging, subjective or complex judgments. The
communication of the critical audit matter does not alter in any way our opinion on the consolidated financial statements,
taken as a whole, and we are not, by communicating the critical audit matter below, providing a separate opinion on the
critical audit matter or on the accounts or disclosures to which it relates.
Valuation of Employee Retirement Plan
Description of
the Matter
The Company maintains a defined benefit plan for employees at its VectivBio entity. At December
31, 2024, the Company’s aggregate defined benefit pension obligation was $18.5 million and
exceeded the fair value of pension plan assets of $15.7 million, resulting in an unfunded defined
benefit pension obligation of $2.8 million. As explained in Note 15 of the consolidated financial
statements, the Company updates the estimates used to measure employee benefit obligations in the
fourth quarter and upon a remeasurement event to reflect the updated actuarial assumptions.
Table of Contents
F-3
Auditing the employee benefit obligation was complex due to the judgment in determining the
discount rate used to measure the pension obligation. This assumption had a significant effect on the
projected benefit obligation. Further, the identified material weakness relating to the financial
statement close process, affected the defined benefit pension obligation and our audit procedures in
this area.
How We
Addressed the
Matter in Our
Audit
To test the discount rate used in the pension obligation, our audit procedures included, among others,
evaluating the methodology used to determine the discount rate with the assistance of an actuarial
specialist. We compared the discount rate used by management to historical trends, current economic
factors and evaluated the change in the discount rate from prior year. In addition, we compared the
discount rate with our independently calculated discount rate as well as with publicly available
comparative rates. The nature and extent of our audit procedures considered the material weakness
described above.
/s/ Ernst & Young LLP
We have served as the Company’s auditor since 1998.
Boston, Massachusetts
March 31, 2025
Table of Contents
F-4
Ironwood Pharmaceuticals, Inc.
Consolidated Balance Sheets
(In thousands, except share and per share amounts)
December 31,
December 31,
2024
2023
ASSETS
Current assets:
Cash and cash equivalents
$
88,559
$
92,154
Accounts receivable, net
81,886
129,122
Prepaid expenses and other current assets
11,923
12,012
Total current assets
182,368
233,288
Property and equipment, net
4,495
5,585
Operating lease right-of-use assets
11,028
12,586
Intangible assets, net
2,860
3,682
Deferred tax assets
144,234
212,324
Other assets
5,923
3,608
Total assets
$
350,908
$
471,073
LIABILITIES AND STOCKHOLDERS' DEFICIT
Current liabilities:
Accounts payable
$
2,127
$
7,830
Accrued research and development costs
6,681
21,331
Accrued expenses and other current liabilities
26,849
44,254
Current portion of operating lease liabilities
3,189
3,126
Current portion of convertible senior notes
—
199,560
Total current liabilities
38,846
276,101
Operating lease obligations, net of current portion
12,304
14,543
Convertible senior notes, net of current portion
198,988
198,309
Revolving credit facility
385,000
300,000
Other liabilities
17,105
28,415
Commitments and contingencies
Stockholders’ deficit:
Preferred stock, $0.001 par value, 75,000,000 shares authorized, no shares issued and
outstanding
—
—
Class A Common Stock, $0.001 par value, 500,000,000 shares authorized and 160,205,899
shares issued and outstanding at December 31, 2024 and 500,000,000 shares authorized and
156,354,238 shares issued and outstanding at December 31, 2023
160
156
Additional paid-in capital
1,395,317
1,355,195
Accumulated deficit
(1,697,735)
(1,698,615)
Accumulated other comprehensive loss
923
(3,031)
Total stockholders’ deficit
(301,335)
(346,295)
Total liabilities and stockholders’ deficit
$
350,908
$
471,073
The accompanying notes are an integral part of these consolidated financial statements.
Table of Contents
F-5
Ironwood Pharmaceuticals, Inc.
Consolidated Statements of Income (Loss)
(In thousands, except per share amounts)
Years Ended December 31,
2024
2023
2022
Revenues:
Collaborative arrangements revenue
$
351,410
$
442,735
$
410,596
Total revenues
351,410
442,735
410,596
Costs and expenses:
Research and development
111,421
116,085
44,265
Selling, general and administrative
144,272
158,314
115,994
Restructuring
2,593
18,317
—
Acquired in-process research and development
—
1,095,449
—
Total costs and expenses
258,286
1,388,165
160,259
Income (loss) from operations
93,124
(945,430)
250,337
Other income (expense):
Interest expense and other financing costs
(33,034)
(21,629)
(7,598)
Interest and investment income
4,468
18,971
9,501
Gain on derivatives
—
19
182
Other
640
—
—
Other income (expense), net
(27,926)
(2,639)
2,085
Income (loss) before income taxes
65,198
(948,069)
252,422
Income tax expense
(64,318)
(83,490)
(77,357)
Net income (loss)
880
(1,031,559)
175,065
Less: Net loss attributable to noncontrolling interests
—
(29,320)
—
Net income (loss) attributable to Ironwood Pharmaceuticals, Inc.
$
880
$
(1,002,239)
$
175,065
Net income (loss) per share attributable to Ironwood Pharmaceuticals,
Inc. stockholders — basic
$
0.01
$
(6.45)
$
1.13
Net income (loss) per share attributable to Ironwood Pharmaceuticals,
Inc. stockholders — diluted
0.01
(6.45)
0.96
Weighted average shares used in computing net income (loss) per share
attributable to Ironwood Pharmaceuticals, Inc. stockholders — basic:
159,083
155,435
154,366
Weighted average shares used in computing net income (loss) per share
attributable to Ironwood Pharmaceuticals, Inc. stockholders — diluted:
160,084
155,435
186,312
The accompanying notes are an integral part of these consolidated financial statements.
Table of Contents
F-6
Ironwood Pharmaceuticals, Inc.
Consolidated Statements of Comprehensive Income (Loss)
(In thousands, except per share amounts)
Years Ended December 31,
2024
2023
2022
Net income (loss) attributable to Ironwood Pharmaceuticals, Inc.
$
880
$
(1,002,239)
$
175,065
Other comprehensive income (loss), net of tax:
Currency translation adjustment
2,901
(2,093)
—
Defined benefit pension plan
1,053
(938)
—
Total other comprehensive income (loss), net of tax
3,954
(3,031)
—
Less: Other comprehensive loss attributable to noncontrolling interest
—
(63)
—
Comprehensive income (loss) attributable to Ironwood Pharmaceuticals, Inc.
$
4,834
$
(1,005,207)
$
175,065
The accompanying notes are an integral part of these consolidated financial statements.
Table of Contents
F-7
Ironwood Pharmaceuticals, Inc.
Consolidated Statements of Stockholders’ Equity (Deficit)
(In thousands, except share amounts)
Accumulated
Ironwood
Class A
Additional
other
Pharmaceuticals, Inc.
Total
Common Stock
paid-in
Accumulated comprehensive
stockholders’
Noncontrolling
stockholders’
Shares
Amount
capital
deficit
loss
equity (deficit)
interests
equity (deficit)
Balance at December 31, 2021
162,036,461
$
162 $1,543,357
$
(937,608) $
—
$
605,911 $
—
$
605,911
Cumulative effect adjustment upon adoption of
ASU 2020-06, net of tax
—
—
(110,217)
66,167
—
(44,050)
—
(44,050)
Issuance of common stock related to share-
based awards and employee stock purchase
plan
2,756,841
3
11,787
—
—
11,790
—
11,790
Share-based compensation expense related to
share-based awards and employee stock
purchase plan
—
—
27,048
—
—
27,048
—
27,048
Repurchases of common stock
(10,766,353)
(11)
(123,375)
—
—
(123,386)
—
(123,386)
Net income
—
—
—
175,065
—
175,065
—
175,065
Balance at December 31, 2022
154,026,949
$
154 $1,348,600
$
(696,376) $
— $
652,378 $
—
$
652,378
Issuance of common stock related to share-
based awards and employee stock purchase
plan
2,327,289
2
4,003
—
—
4,005
—
4,005
Share-based compensation expense related to
share-based awards and employee stock
purchase plan
—
—
32,005
—
—
32,005
—
32,005
Noncontrolling interests on acquisition of
VectivBio Holding AG
—
—
—
—
—
—
26,218
26,218
Purchase of subsidiary shares from
noncontrolling interests
—
—
(29,413)
—
(63)
(29,476)
3,165
(26,311)
Net loss
—
—
—
(1,002,239)
—
(1,002,239)
(29,320)
(1,031,559)
Other comprehensive loss, net of tax
—
—
—
—
(2,968)
(2,968)
(63)
(3,031)
Balance at December 31, 2023
156,354,238
$
156 $1,355,195
$ (1,698,615) $
(3,031) $
(346,295) $
—
$
(346,295)
Issuance of common stock related to share-
based awards and employee stock purchase
plan
3,851,661
4
11,009
—
—
11,013
—
11,013
Share-based compensation expense related to
share-based awards and employee stock
purchase plan
—
—
29,850
—
—
29,850
—
29,850
Taxes paid related to net share settlement of
share-based awards
—
—
(737)
—
—
(737)
—
(737)
Net income
—
—
—
880
—
880
—
880
Other comprehensive income, net of tax
—
—
—
—
3,954
3,954
—
3,954
Balance at December 31, 2024
160,205,899
$
160 $1,395,317
$ (1,697,735) $
923 $
(301,335) $
—
$
(301,335)
The accompanying notes are an integral part of these consolidated financial statements.
Table of Contents
F-8
Ironwood Pharmaceuticals, Inc.
Consolidated Statements of Cash Flows
(In thousands)
Year Ended December 31,
2024
2023
2022
Cash flows from operating activities:
Net income (loss)
$
880
$
(1,031,559)
$
175,065
Adjustments to reconcile net loss to net cash provided by operating activities:
Depreciation and amortization
2,011
1,575
1,418
Loss on disposal of property and equipment
75
—
2
Share-based compensation expense
29,850
32,005
27,048
Change in fair value of note hedge warrants
—
(19)
(182)
Non-cash interest expense
1,904
2,060
1,853
Acquired in-process research and development
—
1,095,449
—
Deferred income taxes
68,090
72,637
65,739
Changes in assets and liabilities:
Accounts receivable, net
47,236
924
7,993
Prepaid expenses and other current assets
89
4,220
3,224
Operating lease right-of-use assets
1,558
1,437
1,327
Other assets
(854)
(319)
153
Accounts payable and accrued expenses
(20,208)
12,380
(8,116)
Accrued research and development costs
(14,650)
(5,875)
(10,638)
Operating lease liabilities
(2,176)
(1,995)
(1,947)
Other liabilities
(10,256)
507
10,824
Net cash provided by operating activities
103,549
183,427
273,763
Cash flows from investing activities:
Purchases of property and equipment
(142)
(273)
(136)
Acquisition of VectivBio Holding AG, net of cash acquired
—
(1,026,045)
—
Net cash used in investing activities
(142)
(1,026,318)
(136)
Cash flows from financing activities:
Proceeds from exercise of stock options and employee stock purchase plan
11,013
6,357
9,540
Taxes paid related to net share settlement of share-based awards
(737)
—
—
Purchase of subsidiary shares from noncontrolling interests
—
(26,311)
—
Repayment of 2024 Convertible Notes
(200,000)
—
—
Repayment of 2022 Convertible Notes
—
—
(120,699)
Proceeds from revolving credit facility
150,000
400,000
—
Costs associated with revolving credit facility
(2,246)
(2,886)
—
Repayments of revolving credit facility
(65,000)
(100,000)
—
Repurchases of common stock
—
—
(126,394)
Net cash provided by (used in) financing activities
(106,970)
277,160
(237,553)
Effect of exchange rate changes on cash, cash equivalents and restricted cash
(32)
(53)
—
Net increase (decrease) in cash, cash equivalents and restricted cash
(3,595)
(565,784)
36,074
Cash, cash equivalents and restricted cash, beginning of period
92,154
657,938
621,864
Cash, cash equivalents and restricted cash, end of period
$
88,559
$
92,154
$
657,938
Reconciliation of cash, cash equivalents, and restricted cash to the consolidated balance sheets
Cash and cash equivalents
$
88,559
$
92,154
$
656,203
Restricted cash
—
—
1,735
Total cash, cash equivalents, and restricted cash
$
88,559
$
92,154
$
657,938
Supplemental cash flow disclosure:
Cash paid for interest
$
32,563
$
13,552
$
5,745
Cash paid for income taxes
$
8,408
$
9,945
$
4,615
Non-cash investing and financing activities
Stock option exercise proceeds receivable in other current assets
$
—
$
—
$
2,351
The accompanying notes are an integral part of these consolidated financial statements.
Table of Contents
F-9
Ironwood Pharmaceuticals, Inc.
Notes to Consolidated Financial Statements
1. Nature of Business
Ironwood Pharmaceuticals, Inc. (“Ironwood” or the “Company”) is a biotechnology company developing and
commercializing life-changing therapies for people living with gastrointestinal (“GI”) and rare diseases. The Company is
focused on the development and commercialization of innovative GI product opportunities in areas of significant unmet need,
leveraging its demonstrated expertise and capabilities in GI diseases.
LINZESS® (linaclotide), the Company’s commercial product, is the first product approved by the United States Food
and Drug Administration (the “U.S. FDA”) in a class of GI medicines called guanylate cyclase type C agonists (“GC-C
agonists”) and is indicated for adult men and women suffering from irritable bowel syndrome with constipation (“IBS-C”) or
chronic idiopathic constipation (“CIC”) and for pediatric patients ages 6-17 years-old suffering from functional constipation
(“FC”). LINZESS is available to adult men and women suffering from IBS-C or CIC in the United States (the “U.S.”) and
Mexico, adult men and women suffering from IBS-C or chronic constipation in Japan, and 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.
The Company has strategic partnerships with leading pharmaceutical companies to support the development and
commercialization of linaclotide throughout the world. The Company and its partner, AbbVie Inc. (together with its affiliates,
“AbbVie”), began commercializing LINZESS in the U.S. in December 2012. Under the Company’s collaboration for North
America with AbbVie, total net sales of LINZESS in the U.S., as recorded by AbbVie, are reduced by commercial costs
incurred by each party, and the resulting amount is shared equally between the Company and AbbVie. Additionally,
development costs are shared equally between the Company and AbbVie.
Outside of the U.S., the Company earns royalties as a percentage of net sales of products containing linaclotide as an
active ingredient by the Company’s collaboration partners. AbbVie has an exclusive license from the Company to develop and
commercialize linaclotide in all countries other than China (including Hong Kong and Macau), Japan and the countries and
territories of North America (the “AbbVie License Territory”). In addition, AbbVie has exclusive rights to commercialize
linaclotide in Canada as CONSTELLA and in Mexico as LINZESS. Astellas Pharma Inc. (“Astellas”), the Company’s partner
in Japan, has an exclusive license to develop, manufacture, and commercialize linaclotide in Japan. AstraZeneca AB (together
with its affiliates) (“AstraZeneca”), the Company’s partner in China, has the exclusive right to develop, manufacture, and
commercialize products containing linaclotide in China (including Hong Kong and Macau) (the “AstraZeneca License
Territory”).
Through the acquisition of VectivBio Holding AG (“VectivBio”), the Company is advancing apraglutide, a next-
generation, synthetic peptide long-acting analog of glucagon-like peptide-2, developed for short bowel syndrome (“SBS”)
patients who are dependent on parenteral support (“PS”). The acquisition of VectivBio is more fully described in Note 3,
Acquisitions, to these consolidated financial statements.
The Company also has IW-3300, a GC-C agonist, for the potential treatment of visceral pain conditions, such as
interstitial cystitis / bladder pain syndrome (“IC/BPS”) and endometriosis. In the fourth quarter of 2024, the Company 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.
The Company was incorporated in Delaware on January 5, 1998 as Microbia, Inc. On April 7, 2008, the Company
changed its name to Ironwood Pharmaceuticals, Inc. To date, the Company has dedicated a majority of its activities to the
research, development and commercialization of linaclotide, as well as to the research and development of its other product
candidates.
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F-10
2. Summary of Significant Accounting Policies
Principles of Consolidation
The accompanying consolidated financial statements as of December 31, 2024 include the accounts of Ironwood, its
wholly-owned subsidiaries, Ironwood Pharmaceuticals Securities Corporation, Ironwood Pharmaceuticals GmbH, VectivBio
AG, and GlyPharma Therapeutic Inc. (“GlyPharma”). All intercompany transactions and balances are eliminated in
consolidation.
For consolidated entities in which the Company owns less than 100% of the outstanding shares, the Company records
net income (loss) and comprehensive income (loss) attributable to noncontrolling interests in its consolidated statements of
income (loss) and comprehensive income (loss), respectively, equal to the percentage of the common stock ownership interest
retained in such entities by the noncontrolling parties. The Company reports noncontrolling interests in consolidated entities as
a component of equity separate from the Company’s equity.
Segment Information
Operating segments are components of an enterprise for which separate financial information is available and is
evaluated regularly by the Company’s chief operating decision-maker in deciding how to allocate resources and in assessing
performance. The Company currently operates in one reportable business segment – human therapeutics. The Company’s
reportable business segment is more fully described in Note 17, Segment Reporting, to these consolidated financial statements.
Reclassifications
Certain prior period financial statement items have been reclassified to conform to current period presentation.
Use of Estimates
The preparation of consolidated financial statements in accordance with U.S. generally accepted accounting
principles requires the Company’s management to make estimates and judgments that may affect the reported amounts of
assets and liabilities and disclosure of contingent assets and liabilities at the date of the consolidated financial statements, and
the amounts of revenues and expenses during the reported periods. On an ongoing basis, the Company’s management
evaluates its estimates, judgments and methodologies. Estimates and assumptions in the consolidated financial statements
include those related to fair value of assets acquired and liabilities assumed in acquisitions; revenue recognition; accounts
receivable; useful lives of long-lived assets; impairment of long-lived assets, including goodwill; valuation procedures for
right-of-use assets and operating lease liabilities; income taxes, including uncertain tax positions and the valuation allowance
for deferred tax assets; research and development expenses; contingencies; defined benefit pension liabilities and certain
investment fund assets; and share-based compensation. The Company bases its estimates on historical experience and on
various other assumptions that are believed to be reasonable, the results of which form the basis for making judgments about
the carrying values of assets and liabilities. Actual results may differ materially from these estimates under different
assumptions or conditions. Changes in estimates are reflected in reported results in the period in which they become known.
Cash and Cash Equivalents
The Company considers all highly liquid investment instruments with a remaining maturity when purchased of three
months or less to be cash equivalents. Investments qualifying as cash equivalents primarily consist of money market funds,
U.S. Treasury securities, and commercial paper. The carrying amount of cash equivalents approximates fair value. The amount
of cash equivalents included in cash and cash equivalents was $55.0 million and $58.7 million at December 31, 2024 and
2023, respectively.
Restricted Cash
The Company is contingently liable under unused letters of credit with a bank, related to the Company’s facility lease
and vehicle lease agreements. Collateral used to secure letters of credit is classified as restricted cash. There was no restricted
cash as of December 31, 2024 or 2023.
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F-11
Concentrations of Suppliers
The Company relies on its collaboration partners and their suppliers to manufacture linaclotide API, linaclotide
finished drug product, and finished goods.
If any of the Company’s collaboration partners and their suppliers were to limit or terminate production or otherwise
fail to meet the quality or delivery requirements needed to satisfy the supply commitments, the process of locating and
qualifying alternate sources could require up to several months, during which time production could be delayed. Such delays
could have a material adverse effect on the Company’s business, financial position and results of operations.
Accounts Receivable
The Company makes judgments as to its ability to collect outstanding receivables and provides an allowance for
credit losses when collection becomes doubtful. Provisions are made based upon a specific review of all significant
outstanding invoices and the overall quality and age of those invoices not specifically reviewed. The Company’s receivables
relate primarily to amounts reimbursed under its collaboration, license, and other agreements. The Company believes that
credit risks associated with these partners are not significant. The Company reviews the need for an allowance for credit losses
for its receivables based on various factors including payment history and historical bad debt experience. The Company had
no allowance for credit losses as of December 31, 2024 or 2023.
Concentrations of Credit Risk
Financial instruments that subject the Company to credit risk primarily consist of cash and cash equivalents,
restricted cash, and accounts receivable. The Company maintains its cash and cash equivalent balances with high-quality
financial institutions and the Company believes that such funds are subject to minimal credit risk. The Company has adopted
an investment policy which limits the amounts the Company may invest in certain types of investments, and requires all
investments held by the Company to be at least A- rated, thereby reducing credit risk exposure.
Accounts receivable primarily consists of amounts due under the linaclotide collaboration agreement with AbbVie for
North America (Note 5). The Company does not obtain collateral for its accounts receivable.
The percentages of revenue recognized from significant collaborative partners of the Company in the years ended
December 31, 2024, 2023, and 2022 and the account receivable balances, net of any payables due, at December 31, 2024 and
2023 are included in the following table:
Accounts
Receivable
Revenue
December 31,
Year Ended December 31,
2024
2023
2024
2023
2022
Collaborative Partner:
AbbVie (North America and Europe)
99 %
87 %
99 %
98 %
98 %
Property and Equipment
Property and equipment, including leasehold improvements, are recorded at cost, and are depreciated when placed
into service using the straight-line method based on their estimated useful lives as follows:
Estimated Useful Life
Asset Description
(In Years)
Laboratory equipment
5
Computer and office equipment
3
Furniture and fixtures
7
Software
3
Included in property and equipment are certain costs of software obtained for internal use. Costs incurred during the
preliminary project stage are expensed as incurred, while costs incurred during the application development
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F-12
stage are capitalized and amortized over the estimated useful life of the software. The Company also capitalizes costs related
to specific upgrades and enhancements when it is probable the expenditures will result in additional functionality.
Maintenance and training costs related to software obtained for internal use are expensed as incurred.
Leasehold improvements are amortized over the shorter of the estimated useful life of the asset or the lease term.
Costs for capital assets not yet placed into service have been capitalized as construction in process, and will be
depreciated in accordance with the above guidelines once placed into service. Maintenance and repair costs are expensed as
incurred.
Intangible Assets
Intangible assets are comprised of the assembled workforce acquired in the VectivBio Acquisition and are amortized
on a straight-line basis over an estimated useful life of five years.
Impairment of Long-Lived Assets
The Company regularly reviews the carrying amount of its long-lived assets to determine whether indicators of
impairment may exist, which warrant adjustments to carrying values or estimated useful lives. If indications of impairment
exist, projected future undiscounted cash flows associated with the asset are compared to the carrying amount to determine
whether the asset’s value is recoverable. If the carrying value of the asset exceeds such projected undiscounted cash flows, the
asset will be written down to its estimated fair value.
Income Taxes
The Company provides for income taxes under the asset and liability method. Deferred tax assets and liabilities are
determined based on differences between financial reporting and tax bases of assets and liabilities and are measured using the
enacted tax rates in effect when the differences are expected to reverse. Deferred tax assets are reduced by a valuation
allowance to reflect the uncertainty associated with their ultimate realization.
The Company accounts for uncertain tax positions recognized in the consolidated financial statements in accordance
with the provisions of Accounting Standards Codification (“ASC”) Topic 740, Income Taxes, by prescribing a more-likely-
than-not threshold for financial statement recognition and measurement of a tax position taken or expected to be taken in a tax
return. When uncertain tax positions exist, the Company recognizes the tax benefit of tax positions to the extent that the
benefit will more likely than not be realized. The determination as to whether the tax benefit will more likely than not be
realized is based upon the technical merits of the tax position as well as consideration of the available facts and circumstances.
The Company evaluates uncertain tax positions on a quarterly basis and adjusts the level of the liability to reflect any
subsequent changes in the relevant facts surrounding the uncertain positions. Any changes to these estimates, based on the
actual results obtained and/or a change in assumptions, could impact the Company’s income tax provision in future periods.
Interest and penalty charges, if any, related to unrecognized tax benefits are classified as income tax expense in the Company’s
consolidated statements of income (loss).
Financing Costs
Financing costs include costs directly attributable to the Company’s offerings of its equity securities and its debt
financings. Costs attributable to equity offerings are charged as a reduction to stockholders’ equity against the proceeds of the
offering once the offering is completed. Costs attributable to debt financings are deferred and amortized to interest expense
over the term of the debt using the effective interest method. In accordance with ASC Topic 835, Interest, the Company
presents on its balance sheet unamortized debt issuance costs related to convertible notes as a direct deduction from the
associated debt liability and unamortized debt issuance costs related to revolving credit arrangements as other assets.
Leases
The Company’s lease portfolio for the year ended December 31, 2024 included: an office lease for its headquarters
location and other locations, vehicle leases for its salesforce representatives, and leases for computer and
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F-13
office equipment. The Company determines if an arrangement is a lease at the inception of the contract and determines the
classification of its leases at lease commencement. The asset component of the Company’s operating leases is recorded as
operating lease right-of-use assets, and the liability component is recorded as current portion of operating lease liabilities and
operating lease liabilities, net of current portion in the Company’s consolidated balance sheets. As of December 31, 2024, the
Company did not record any finance leases.
Right-of-use assets and operating lease liabilities are recognized based on the present value of lease payments over
the lease term at the lease commencement date. The lease term used to measure the right-of-use asset and operating lease
liability may include options to extend the lease when it is reasonably certain that the Company will exercise the option. The
Company accounts for lease components and non-lease components together as a single lease component for the asset class of
right-of-use real estate assets. The Company uses an incremental borrowing rate based on the information available at lease
commencement in determining the present value of lease payments, if an implicit rate of return is not readily determinable.
Operating lease right-of-use assets are adjusted for prepaid rent, initial direct costs, and lease incentives.
Right-of-use assets and operating lease liabilities are remeasured upon reassessment events and modifications to
leases using the present value of remaining lease payments and estimated incremental borrowing rate at the time of
remeasurement, as applicable.
Operating lease cost is recognized on a straight-line basis over the lease term, and includes amounts related to short-
term leases. The Company has elected to not recognize lease terms with a term of twelve months or less on its balance sheet
for all classes of underlying asset types. The Company recognizes variable lease payments as operating expenses in the period
in which the obligation for those payments is incurred. Variable lease payments primarily include common area maintenance,
utilities, real estate taxes, insurance, and other operating costs that are passed on from the lessor in proportion to the space
leased by the Company.
Derivative Assets and Liabilities
In June 2015, the Company issued 2.25% Convertible Senior Notes due June 15, 2022 (the “2022 Convertible
Notes”), and in August 2019, the Company issued 0.75% Convertible Senior Notes due 2024 (the “2024 Convertible Notes”)
and 1.50% Convertible Senior Notes due 2026 (the “2026 Convertible Notes”, and together with the 2022 Convertible Notes
and the 2024 Convertible Notes, the “Convertible Senior Notes”). In connection with the issuance of the 2022 Convertible
Notes, the Company entered into convertible note hedge transactions (the “Convertible Note Hedges”) and separate note
hedge warrant transactions (the “Note Hedge Warrants”), with certain financial institutions (Note 10). In connection with the
partial repurchase of the 2022 Convertible Notes in August 2019, the Company terminated its Convertible Note Hedges and
Note Hedge Warrants proportionately. The Convertible Note Hedges terminated unexercised upon expiry in June 2022 and the
Note Hedge Warrants terminated unexercised upon expiry in April 2023. These instruments are derivative financial
instruments under ASC Topic 815, Derivatives and Hedging (“ASC 815”).
These derivatives are recorded as assets or liabilities at fair value each reporting date and the fair value is determined
using the Black-Scholes option-pricing model. The changes in fair value are recorded as a component of other (expense)
income in the consolidated statements of income. Significant inputs used to determine the fair value include the price per
share of the Company’s Class A Common Stock, expected terms of the derivative instruments, strike prices of the derivative
instruments, risk-free interest rates, and expected volatility of the Company’s Class A Common Stock. Changes to these inputs
could materially affect the valuation of the derivative instruments. Cash flows related to the purchase and settlement of
derivatives are classified as financing activities and gains and losses upon revaluation and settlement are classified as
operating activities on the consolidated statement of cash flows.
In August 2019, in connection with the issuance of the 2024 Convertible Notes and the 2026 Convertible Notes, the
Company entered into the Capped Calls. The Capped Calls cover the same number of shares of Class A Common Stock that
initially underlie the 2024 Convertible Notes and the 2026 Convertible Notes (subject to anti-dilution and certain other
adjustments). These instruments meet the conditions outlined in ASC 815 to be classified in stockholders’ equity (deficit) and
are not subsequently remeasured as long as the conditions for equity classification continue to be met. The Capped Calls
related to the 2024 Convertible Notes expired unexercised upon maturity of the 2024 Convertible Notes in June 2024.
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F-14
Share Repurchases
The Company accounts for repurchases of its Class A Common Stock on the trade date by recording the excess of the
repurchase price over the par value entirely to additional paid-in capital. All repurchased shares are retired or constructively
retired. Issued and outstanding shares are reduced by shares repurchased.
Revenue Recognition
The Company’s revenues are generated primarily through collaborative arrangements and license agreements related
to the research and development and commercialization of linaclotide. The terms of the collaborative research and
development, license, co-promotion and other agreements contain multiple performance obligations which may include (i)
licenses, (ii) research and development activities, including participation on joint steering committees, (iii) the manufacture of
finished drug product, API, or development materials for a partner, which are reimbursed at a contractually determined rate,
and (iv) education or co-promotion activities by the Company’s clinical sales specialists. Non-refundable payments to the
Company under these agreements may include (i) up-front license fees, (ii) payments for research and development activities,
(iii) payments for the manufacture of finished drug product, API, or development materials, (iv) payments based upon the
achievement of certain milestones, (v) payments for sales detailing, promotional support services and medical education
initiatives, and (vi) royalties on product sales. The Company receives its share of the net profits or bears its share of the net
losses from the sale of linaclotide in the U.S. through its collaboration agreement with AbbVie for North America. The
Company has adopted a policy to recognize revenue net of tax withholdings, as applicable.
Collaboration, License, and Other Commercial Agreements
Upon licensing intellectual property to a customer, the Company determines if the license is distinct from the other
performance obligations identified in the arrangement. The Company recognizes revenues from the transaction price,
including non-refundable, up-front fees allocated to the license when the license is transferred to the customer if the license
has distinct benefit to the customer. For licenses that are combined with other promises, the Company assesses the nature of
the combined performance obligation to determine whether the combined performance obligation is satisfied over time or at a
point in time. For performance obligations that are satisfied over time, the Company evaluates the measure of progress each
reporting period and, if necessary, adjusts the measure of performance and related revenue recognition.
The Company’s license and collaboration agreements include milestone payments, such as development and other
milestones. The Company evaluates whether the milestones are considered probable of being reached and estimates the
amount to be included in the transaction price using the most likely amount method at the inception of the agreement. If it is
probable that a significant revenue reversal would not occur, the associated milestone value is included in the transaction
price. Milestone payments that are not within the control of the Company, such as regulatory approvals, are not considered
probable of being achieved until those approvals are received. The transaction price is then allocated to each performance
obligation on a relative standalone selling price basis, for which the Company recognizes revenue as or when the performance
obligations under the contract are satisfied. The Company re-evaluates the probability of achievement of such milestones and
any related constraint at each reporting period, and any adjustments are recorded on a cumulative catch-up basis.
Agreements that include the supply of API or drug product for either clinical development or commercial supply at
the customer’s discretion are generally considered as options. The Company assesses if these options provide a material right
to its partner, and if so, they are accounted for as separate performance obligations. If the Company is entitled to additional
payments when the customer exercises these options, any additional payments are recorded as revenue when the customer
obtains control of the goods, which is typically upon shipment for sales of API and finished drug product.
For agreements that include sales-based royalties, including milestone payments based on the level of sales, and the
license is deemed to be the predominant item to which the royalties relate, the Company recognizes revenue when the related
sales occur in accordance with the sales-based royalty exception.
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F-15
Net Profit or Net Loss Sharing
In accordance with ASC Topic 808, Collaborative Arrangements (“ASC 808”), the Company considers the nature
and contractual terms of the arrangement and the nature of the Company’s business operations to determine the classification
of payments under the Company’s collaboration agreements. While ASC 808 provides guidance on classification, the standard
is silent on matters of separation, initial measurement, and recognition. Therefore, the Company applies the separation, initial
measurement, and recognition principles of ASC Topic 606, Revenue from Contracts with Customers (“ASC 606”), as
applicable.
The Company’s collaborative arrangements revenues generated from sales of LINZESS in the U.S. are considered
akin to sales-based royalties. In accordance with the sales-based royalty exception, the Company recognizes its share of the
pre-tax commercial net profit or net loss generated from the sales of LINZESS in the U.S. in the period the product sales are
earned, as reported by AbbVie, and related cost of goods sold and selling, general and administrative expenses as incurred by
the Company and AbbVie. These amounts are partially determined based on amounts provided by AbbVie and involve the use
of estimates and judgments, such as product sales allowances and accruals related to prompt payment discounts, chargebacks,
governmental and contractual rebates, wholesaler fees, product returns, and co-payment assistance costs, which could be
adjusted based on actual results in the future. The Company is highly dependent on AbbVie for timely and accurate
information regarding net revenues from sales of LINZESS in the U.S. in accordance with both ASC 808 and ASC 606, and
the related costs, in order to accurately report its results of operations. If the Company does not receive timely and accurate
information or incorrectly estimates activity levels associated with the collaboration at a given point in time, the Company
could be required to record adjustments in future periods.
In accordance with ASC 606-10-55, Principal Agent Considerations, the Company records revenue transactions as
net product revenue in its consolidated statements of income if it is deemed the principal in the transaction, which includes
being the primary obligor, retaining inventory risk, and control over pricing. Given that the Company is not the primary
obligor and does not have the inventory risks in the collaboration agreement with AbbVie for North America, it records its
share of the net profits or net losses from the sales of LINZESS in the U.S. on a net basis and presents the settlement payments
to and from AbbVie as collaboration expense or collaborative arrangements revenue, as applicable. The Company and AbbVie
settle the cost sharing quarterly such that the Company’s statements of income reflect 50% of the pre-tax net profit or loss
generated from sales of LINZESS in the U.S.
Other
The Company’s deferred revenue balance consists of advance billings and payments received from collaboration
partners in excess of revenue recognized.
Research and Development Costs
The Company generally expenses research and development costs to operations as incurred. The Company
capitalizes nonrefundable advance payments made by the Company for research and development activities and defers
expense recognition until the related goods are received or the related services are performed.
Research and development expenses are comprised of costs incurred in performing research and development
activities, including salary, benefits, share-based compensation, and other employee-related expenses; laboratory supplies and
other direct expenses; facilities expenses; overhead expenses; third-party contractual costs relating to nonclinical studies and
clinical trial activities and related contract manufacturing expenses, development of manufacturing processes and regulatory
registration of third-party manufacturing facilities; licensing fees for the Company’s product candidates; and other outside
expenses.
The Company has certain collaboration agreements pursuant to which it shares or has shared research and
development expenses related to linaclotide. The Company records expenses incurred under such linaclotide collaboration
arrangements as research and development expense. Under the Company’s collaboration agreement with AbbVie for North
America, the Company is reimbursed for certain research and development expenses and nets these reimbursements against its
research and development expenses as incurred.
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F-16
Research and development expense includes up-front payment, non-contingent payment, and milestone payment
obligations under certain collaboration arrangements. Expense is recognized when the obligation is determined to be probable.
Restructuring Expenses
Restructuring expenses are comprised primarily of costs associated with exit and disposal activities in accordance
with ASC Topic 420, Exit or Disposal Cost Obligations, and ASC Topic 712, Compensation – Nonretirement Postemployment
Benefits, and include one-time termination benefits and contract-related costs. Such costs are based on estimates of fair value
in the period liabilities are incurred. The Company evaluates and adjusts these costs for changes in circumstances as additional
information becomes available.
Selling, General and Administrative Expenses
The Company expenses selling, general and administrative costs to operations as incurred. Selling, general and
administrative expenses consist primarily of compensation, benefits and other employee-related expenses for personnel in the
Company’s administrative, finance, legal, information technology, business development, commercial, sales, marketing,
communications and human resource functions. Other costs include legal costs of pursuing patent protection of the Company’s
intellectual property, general and administrative related facility costs, insurance costs and professional fees for accounting, tax,
consulting, legal and other services.
The Company includes AbbVie’s selling, general and administrative cost-sharing payments in the calculation of the
net profits and net losses from the sale of LINZESS in the U.S. and presents the net payment to or from AbbVie as
collaboration expense or collaborative arrangements revenue, respectively.
Defined Benefit Pension Obligations
Pension benefits earned during the year, as well as interest on projected benefit obligations, are accrued. Service costs
are recognized within research and development expenses or selling, general and administrative expenses, depending on the
function of the plan participant. Prior service costs and credits resulting from changes in plan benefits are generally amortized
over the average remaining service period of the employees expected to receive benefits. Actuarial gains and losses are
recognized in other income (expense), net, in the year in which they occur. The Company recognizes a pension plan’s funded
status as either an asset or liability in its consolidated balance sheets.
Share-Based Compensation Expense
The Company grants awards under its share-based compensation programs, including stock awards, restricted stock
awards (“RSAs”), restricted stock units (“RSUs”) (including both time-based and performance-based RSUs), stock options,
and shares issued under the Company’s employee stock purchase plan (“ESPP”). Share-based compensation is recognized as
expense in the consolidated statements of income based on the grant date fair value over the requisite service period, net of
estimated forfeitures. The Company estimates forfeitures over the requisite service period using historical forfeiture activity
and records share-based compensation expense only for those awards that are expected to vest.
The Company estimates the fair value of stock options using the Black-Scholes option-pricing model, which requires
the use of subjective assumptions including volatility and expected term, among others. The fair value of stock awards, RSAs,
and RSUs is based on the market value of the Company’s Class A Common Stock on the date of grant, with the exception of
performance-based RSUs with market conditions, which are measured using the Monte Carlo simulation method on the date
of grant (Note 13). Discounted stock purchases under the Company’s ESPP are valued on the first date of the offering period
using the Black-Scholes option-pricing model to compute the fair value of the lookback provision plus the purchase discount.
For awards that vest based on service conditions and market conditions, the Company uses a straight-line method to
recognize compensation expense over the respective service period. For awards that contain performance conditions, the
Company determines the appropriate amount to expense at each reporting date based on the anticipated achievement of
performance targets, which requires judgement, including forecasting the achievement of future specified targets. At the date
performance conditions are determined to be probable of achievement, the Company
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F-17
records a cumulative expense catch-up, with remaining expense amortized over the remaining service period. Throughout the
performance period, the Company re-assesses the estimated performance and updates the number of performance-based
awards that it believes will ultimately vest. Discounted stock purchases under the Company’s ESPP are recognized over the
offering period.
Compensation expense related to modified awards is measured based on the fair value for the awards as of the
modification date. Any incremental compensation expense arising from the excess of the fair value of the awards on the
modification date compared to the fair value of the awards immediately before the modification date is recognized at the
modification date or ratably over the requisite remaining service period, as appropriate.
While the assumptions used to calculate and account for share-based compensation awards represent management’s
best estimates, these estimates involve inherent uncertainties and the application of management’s judgment. As a result, if
revisions are made to the Company’s underlying assumptions and estimates, the Company’s share-based compensation
expense could vary significantly from period to period.
Patent Costs
The Company incurred and recorded as operating expense legal and other fees related to patents of $2.2 million, $1.8
million, and $1.3 million for the years ended December 31, 2024, 2023 and 2022, respectively. These costs were charged to
selling, general and administrative expenses as incurred.
Net Income (Loss) Per Share
Basic net income (loss) per common share is computed by dividing the net income by the weighted average number
of common shares outstanding during the period. Diluted net income (loss) per share reflects the potential dilution beyond
common shares for basic net income (loss) per share that could occur if securities or other contracts to issue common shares
were exercised, converted into common shares, or resulted in the issuance of common shares that would have shared in the
Company’s earnings.
Foreign Currency Translation
For subsidiaries with a different functional currency than the U.S. dollar, assets and liabilities are translated at the
exchange rate as of the balance sheet date and income and expense items are translated at the average exchange rate for the
reporting period. Adjustments resulting from the translation of the financial statements of foreign subsidiaries are recorded in
accumulated comprehensive income (loss), a separate component of stockholders’ equity.
Acquisitions
The Company evaluates acquisitions of assets and other similar transactions to assess whether the transaction should
be accounted for as a business combination or asset acquisition by first applying a screen test to determine whether
substantially all of the fair value of the gross assets acquired is concentrated into a single identifiable asset or group of similar
identifiable assets. If the screen test is met, a single asset or group of assets is not a business and is accounted for as an asset
acquisition. If the screen test is not met, further determination is required as to whether the Company has acquired inputs and
processes that have the ability to create outputs that would meet the requirements of a business.
The Company accounts for business combinations using the acquisition method of accounting, which requires the
acquiring entity to recognize the fair value of assets acquired and liabilities assumed and establishes the acquisition date as the
fair value measurement point. The Company determines the fair value of assets acquired and liabilities assumed based on
management’s estimate of the fair value of assets acquired and liabilities assumed in the acquisition. Goodwill represents the
excess of the purchase price over the fair value of the net tangible and intangible assets acquired. Transaction costs are
expensed as incurred.
The Company accounts for asset acquisitions that are not determined to be a business combination by recognizing net
assets based on the consideration paid, inclusive of transaction costs, on a relative fair value basis. In an asset acquisition, the
cost allocated to acquired in-process research and development (“IPR&D”) with no alternative future use is charged to
research and development expense at the acquisition date. The Company classifies asset acquisitions of acquired IPR&D as
investing activities on its consolidated statements of cash flows.
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F-18
Comprehensive Income (Loss)
Comprehensive income (loss) is comprised of net income (loss) and other comprehensive income (loss). Other
comprehensive income (loss) includes foreign currency translation adjustments and certain changes in the fair value of
pension plan assets and projected benefit obligation attributed to the Company’s defined benefit pension plans. Accumulated
other comprehensive income (loss) is presented as a separate component of stockholders’ equity (deficit).
Subsequent Events
The Company considers events or transactions that have occurred after the balance sheet date of December 31, 2024,
but prior to the filing of the financial statements with the Securities and Exchange Commission (“SEC”) to provide additional
evidence relative to certain estimates or to identify matters that require additional recognition or disclosure. Subsequent events
have been evaluated through the filing of the financial statements accompanying this Annual Report on Form 10-K. Refer to
Note 16 for subsequent events relating to workforce reductions and restructuring.
New Accounting Pronouncements
From time to time, new accounting pronouncements are issued by the Financial Accounting Standards Board (the
“FASB”) or other standard setting bodies that are adopted by the Company as of the specified effective date. The Company
did not adopt any new accounting pronouncements during the year ended December 31, 2024 that had a material effect on its
consolidated financial statements.
In November 2023, the FASB issued Accounting Standards Update (“ASU”) No. 2023-07, Segment Reporting (Topic
280) (“ASU 2023-07”). The guidance in ASU 2023-07 expands prior reportable segment disclosure requirements by requiring
entities to disclose significant segment expenses that are regularly provided to the Chief Operating Decision Maker
(“CODM”) and details of how the CODM uses financial reporting to assess their segment’s performance. The standard is
effective for fiscal years beginning after December 15, 2023 and interim periods within fiscal years beginning after December
15, 2024, with early adoption permitted. The ASU is required to be applied retrospectively upon adoption. The expanded
disclosure requirements are included in the consolidated financial statements (Note 17).
In December 2023, the FASB issued ASU No. 2023-09, Income Taxes (Topic 740): Improvements to Income Tax
Disclosures (“ASU 2023-09”). The guidance in ASU 2023-09 improves the transparency of annual income tax disclosures by
requiring greater disaggregation of information in the rate reconciliation and income taxes paid disaggregated by jurisdiction.
The standard is effective for fiscal years beginning after December 15, 2024, with early adoption permitted. Upon adoption,
ASU 2023-09 may be applied prospectively or retrospectively. The Company is currently evaluating the impact that the
adoption of ASU 2023-09 may have on its disclosures in its annual consolidated financial statements.
In November 2024, the FASB issued ASU No. 2024-03, Disaggregation of Income Statement Expenses (“ASU 2024-
03”). The guidance in ASU 2024-03 requires new financial statement disclosures in tabular format, disaggregating information
about prescribed categories underlying any relevant income statement expense captions. The standard is effective for fiscal
years beginning after December 15, 2026 and interim periods within fiscal years beginning after December 15, 2027, with
early adoption permitted. Upon adoption, ASU 2024-03 may be applied prospectively or retrospectively. The Company is
currently evaluating the impact that the adoption of ASU 2024-03 may have on its disclosures in its consolidated financial
statements.
In November 2024, the FASB issued ASU No. 2024-04, Debt—Debt with Conversion and Other Options (Subtopic
470-20) (“ASU 2024-04”). The guidance in ASU 2024-04 clarifies the requirements related to accounting for the settlement of
a debt instrument as an induced conversion. The standard is effective for fiscal years beginning after December 15, 2025, and
interim periods within fiscal years beginning after December 15, 2025, with early adoption permitted as of the beginning of a
reporting period if the entity has also adopted ASU 2020-06 for that period. The Company is currently evaluating the impact
that the adoption of ASU 2024-04 may have on its disclosures in its consolidated financial statements.
Other recent accounting pronouncements issued, but not yet effective, are not expected to be applicable to the
Company or have a material effect on the consolidated financial statements upon future adoption.
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F-19
During the year ended December 31, 2022, the Company adopted the following accounting pronouncement that had
a material effect on its consolidated financial statements:
In August 2020, the FASB issued ASU No. 2020-06, Debt—Debt with Conversion and Other Options (Subtopic 470-
20) and Derivatives and Hedging— Contracts in Entity’s Own Equity (Subtopic 815-40): Accounting for Convertible
Instruments and Contracts in an Entity’s Own Equity (“ASU 2020-06”). The amendments in ASU 2020-06 simplify the
accounting for certain financial instruments with characteristics of liabilities and equity, including convertible instruments and
contracts on an entity’s own equity. Under ASU 2020-06, embedded conversion features are no longer separately reported in
equity and convertible debt instruments are now accounted for as a single liability measured at amortized cost, as long as no
other features require bifurcation and recognition as derivatives. These changes reduce reported interest expense and increase
reported net income for entities with convertible instruments that were bifurcated between liabilities and equity under
previously existing guidance. Additionally, temporary differences between the book and tax bases resulting from the
bifurcation of the embedded conversion feature under previously existing guidance have been eliminated and deferred tax
assets and liabilities arising from such temporary differences are no longer reported. The new guidance also requires the if-
converted method to be used in diluted earnings per share computations for all convertible instruments and revised the if-
converted method to preclude the addback of interest expense to the numerator if the principal portions of the convertible
instruments are required to be settled in cash. The standard became effective for public companies for fiscal years, and interim
periods within those fiscal years, beginning after December 15, 2021. Upon adoption, entities could elect to apply the new
standard on a modified retrospective or full retrospective basis.
The Company adopted ASU 2020-06 on January 1, 2022 using the modified retrospective approach, which resulted
in a cumulative-effect adjustment recorded on the date of adoption as follows (in thousands):
December 31, 2021
Effect of the Adoption
January 1, 2022
Consolidated Balance Sheet
As Reported
of ASU 2020-06
As Adjusted
Deferred tax assets
$
333,294
$
16,855
$
350,149
Current portion of convertible senior notes
116,858
3,581
120,439
Long-term portion of convertible senior notes
337,333
57,324
394,657
Additional paid-in-capital
1,543,357
(110,217)
1,433,140
Retained earnings
(937,608)
66,167
(871,441)
Interest expense recognized in subsequent periods is reduced as a result of accounting for convertible debt
instruments as a single liability measured at amortized cost, with a decrease of $22.1 million of non-cash interest expense
during the year ended December 31, 2022 compared to the year ended December 31, 2021 related to convertible debt
instruments outstanding on the adoption date.
The adoption of ASU 2020-06 did not impact the Company’s liquidity or cash flows.
3. Acquisitions
In June 2023, the Company completed a tender offer to purchase 98% of the outstanding ordinary shares of
VectivBio, a clinical-stage biotechnology company focused on the discovery and development of treatments for severe, rare
GI conditions for which there is a significant unmet medical need, at a price per share of $17.00, net to the shareholders of
VectivBio in cash, without interest and subject to any applicable withholding taxes (the “VectivBio Acquisition”). In
December 2023, the Company completed a squeeze-out merger under Swiss law to acquire all remaining outstanding ordinary
shares in cash at a price per share of $17.00, totaling $26.3 million, and VectivBio Holding AG was merged with and into
Ironwood Pharmaceuticals GmbH, a wholly-owned subsidiary of Ironwood organized under the laws of Switzerland (the
“Squeeze-out Merger”). The aggregate consideration paid by the Company to acquire the shares accepted for payment was
approximately $1.2 billion. The Company financed the acquisition through proceeds from the borrowings under the Revolving
Credit Agreement (as defined elsewhere below) and cash on hand. As of December 31, 2023, there was no remaining
noncontrolling interest in VectivBio.
The total purchase consideration for VectivBio is as follows (in thousands):
Cash consideration paid to selling shareholders (1)
$
1,041,391
Cash consideration paid to settle VectivBio restricted stock units (“RSUs”) and stock options (2)
78,003
Cash consideration paid to settle VectivBio warrants (3)
3,720
Transaction costs
26,270
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F-20
Fair value of noncontrolling interest (4)
26,218
Total purchase consideration
$
1,175,602
(1) The cash consideration paid to selling shareholders was determined based on the total number of the outstanding ordinary
shares of VectivBio (the “VectivBio Shares”) tendered at closing of 61,258,315 at a per share price of $17.00.
(2) The cash consideration paid to settle VectivBio RSUs and stock options issued under VectivBio’s equity incentive plans
was determined based on the total number of underlying VectivBio Shares of 8,904,171 at a per share price of $17.00, less
the exercise price for stock options.
(3) The cash consideration paid to settle VectivBio warrants was determined based on the total number of VectivBio warrant
shares outstanding at close of 324,190 at a per share price of $11.4757 calculated as the per share price of $17.00, less the
exercise price of $5.5243 per share.
(4) The fair value of the noncontrolling interest was determined based on the total number of VectivBio Shares outstanding at
closing of 1,547,723 at the closing date of the tender offer, using the VectivBio closing share price on June 28, 2023 of
$16.94.
The VectivBio Acquisition was accounted for as an asset acquisition under Accounting Standards Codification
(“ASC”) Topic 805, Business Combinations, because substantially all of the fair value of the gross assets acquired was
concentrated in a single identifiable in-process research and development (“IPR&D”) asset, apraglutide, VectivBio’s lead
investigational asset. Apraglutide is a next generation, long-acting synthetic GLP-2 analog being developed for SBS patients
who are dependent on PS. The Company recognized the acquired assets and assumed liabilities based on the consideration
paid, inclusive of transaction costs, on a relative fair value basis. In accordance with the accounting for asset acquisitions, an
entity that acquires IPR&D assets in an asset acquisition follows the guidance in ASC Topic 730, Research and Development,
which requires that both tangible and intangible identifiable research and development assets with no alternative future use be
allocated a portion of the consideration transferred and recorded as research and development expense at the acquisition date.
As a result, the Company recorded approximately $1.1 billion in acquired IPR&D expense related to the apraglutide IPR&D
asset during the second quarter of 2023.
The following is the allocation of the purchase consideration based on the relative fair value of assets acquired and
liabilities assumed by the Company (in thousands):
Assets acquired
Cash and cash equivalents
$
123,340
Prepaid expenses and other current assets
10,867
Property and equipment
126
Intangible assets
4,100
Acquired in-process research and development
1,095,449
Total assets acquired
$
1,233,882
Liabilities assumed
Current liabilities
42,377
Other liabilities
15,903
Total liabilities assumed
$
58,280
Net assets acquired
$
1,175,602
Acquisition-related expenses include direct and incremental costs incurred in connection with the transaction,
including integration-related professional services and employee retention-related benefits. Acquisition-related expenses
exclude transaction costs included in the computation of total consideration paid. The Company tracked and disclosed
acquisition-related expenses incurred through the end of the second quarter of 2024. For the six months ended June 30, 2024,
the Company incurred acquisition related expenses of $3.6 million, of which $1.1 million was included in selling, general, and
administrative expenses and $2.5 million was included in restructuring expenses within the Company’s consolidated statement
of income (loss). The Company incurred acquisition-related expenses of $55.6 million for the year ended December 31, 2023,
of which $25.6 million was included in selling, general and administrative expenses, $15.1 million was included in research
and development expense, and $14.9 million was included in restructuring expense within the Company’s consolidated
statement of income (loss) for the year ended December 31, 2023.
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F-21
Intangible assets are comprised of the assembled workforce and are amortized on a straight-line basis over an
estimated useful life of five years. The Company recognized $0.8 million of amortization expense during the year ended
December 31, 2024. The Company recognized $0.4 million of amortization expense during the period between acquisition
date on June 29, 2023 through December 31, 2023. The net carrying value of the assembled workforce at December 31, 2024
is $2.9 million. Future annual amortization expense will be $0.8 million for each of the years ended December 31, 2025
through December 31, 2027 and $0.4 million for the year ending December 31, 2028.
4. Net Income (Loss) Per Share
The following table sets forth the computation of basic and diluted net income (loss) per common share (in
thousands, except per share amounts):
Year Ended December 31,
2024
2023 (1)
2022
Numerator:
Net income (loss)
$
880
$ (1,031,559)
$ 175,065
Less: Net loss attributable to noncontrolling interests
—
(29,320)
—
Net income (loss) attributable to Ironwood Pharmaceuticals, Inc.
880
(1,002,239)
175,065
Add back interest expense, net of tax benefit, on assumed conversion of
2024 Convertible Notes
—
—
1,781
Add back interest expense, net of tax benefit, on assumed conversion of
2026 Convertible Notes
—
—
2,668
Numerator used in computing net income (loss) per share — diluted
$
880
$ (1,002,239)
$ 179,514
Denominator:
Weighted average number of common shares outstanding used in computing
net income (loss) per share — basic
159,083
155,435
154,366
Effect of dilutive securities:
Stock options
—
—
306
Time-based restricted stock units
425
—
1,375
Performance-based restricted stock units
480
—
282
Restricted stock
96
—
115
2024 Convertible Notes assumed conversion
—
—
14,934
2026 Convertible Notes assumed conversion
—
—
14,934
Dilutive potential common shares
Weighted average number of common shares outstanding used in computing
net income (loss) per share — diluted
160,084
155,435
186,312
Net income (loss) per share — basic
$
0.01
$
(6.45)
$
1.13
Net income (loss) per share — diluted
$
0.01
$
(6.45)
$
0.96
(1) The Company incurred a net loss during the year ended December 31, 2023 and therefore did not differentiate basic and diluted earnings per share, as the
effect of dilutive securities would be anti-dilutive.
The dilutive impact of the Convertible Senior Notes is determined using the if-converted method. Under the if-
converted method, the Convertible Senior Notes are assumed to be converted into common stock at the beginning of the
period (or at the time of issuance, if later). Interest charges are deducted from the numerator, unless the principal amount of
the convertible instruments is required to be paid in cash. The dilutive impact of all other types of dilutive securities is
determined using the treasury stock method.
The outstanding securities set forth in the following table have been excluded from the computation of diluted
weighted average shares outstanding, as applicable, as their effect would be anti-dilutive (in thousands):
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F-22
Year Ended December 31,
2024
2023
2022
Stock options
4,821
4,829
6,152
Time-based restricted stock units
3,596
28
10
Performance-based restricted stock units
34
216
1,182
Note Hedge Warrants
—
2,514
8,318
2026 Convertible Notes
14,934
—
—
Total
23,385
7,587
15,662
There was no dilutive impact of the 2024 Convertible Notes (as defined below) and the 2022 Convertible Notes for
the year ended December 31, 2024 and December 31, 2022, respectively, because the Company had elected prior to the
beginning of the period to settle the conversion of 2024 Convertible Notes and 2022 Convertible Notes, if any, with a
combination settlement of a cash payment equal to the principal value of converted notes and shares of Class A Common
Stock equal to the conversion value in excess of the principal value, if any (Note 10). Accordingly, interest expense was not
removed from the numerator and there was no calculated spread added to the denominator because the average market price of
the Company’s Class A common stock during the portion of each period in which the 2024 Convertible Notes and the 2022
Convertible Notes were outstanding was not in excess of the conversion price.
5. Collaboration, License, and Other Agreements
The Company has linaclotide collaboration agreements with AbbVie for North America and AstraZeneca for China
(including Hong Kong and Macau), as well as linaclotide license agreements with Astellas for Japan and with AbbVie for the
AbbVie License Territory. The following table provides amounts included in the Company’s consolidated statements of
income (loss) as collaborative arrangements revenue attributable to transactions from these and other agreements (in
thousands):
Year Ended December 31,
Collaborative Arrangements Revenue
2024
2023
2022
Linaclotide Collaboration and License Agreements:
AbbVie (North America)
$
343,154 $
433,242 $
401,498
AbbVie (Europe and other)
3,236
2,779
2,444
AstraZeneca (China, including Hong Kong and Macau)
364
430
635
Astellas (Japan)
1,673
1,799
2,001
Other Agreements:
Alnylam (GIVLAARI)
—
—
2,194
Asahi Kasei Pharma Corporation (apraglutide)
2,249
2,009
—
Other
734
2,476
1,824
Total collaborative arrangements revenue
$
351,410
$
442,735
$
410,596
Accounts receivable, net, included $81.9 million and $129.1 million primarily related to collaborative arrangements
revenue, collectively, as of December 31, 2024 and 2023, respectively. Accounts receivable, net, included $81.3 million and
$112.6 million due from the Company’s partner, AbbVie, net of $3.1 million and $4.3 million of accounts payable, as of
December 31, 2024 and 2023, respectively.
The Company routinely assesses the creditworthiness of its license and collaboration partners. The Company did not
experience any material losses related to receivables from its license or collaboration partners during the years ended
December 31, 2024, 2023, or 2022.
Linaclotide Agreements
Collaboration Agreement for North America with AbbVie
In September 2007, the Company entered into a collaboration agreement with AbbVie to develop and commercialize
linaclotide for the treatment of IBS-C, CIC, and other GI conditions in North America. Under the terms of this collaboration
agreement, the Company received an upfront licensing fee, equity investment, and development and
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F-23
regulatory milestones, and shares 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, the Company receives 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.
During the years ended December 31, 2024, 2023, and 2022, the Company incurred $7.4 million, $7.0 million, and
$8.0 million, respectively, in total research and development expenses under the linaclotide collaboration for North America.
As a result of the research and development cost-sharing provisions of the linaclotide collaboration for North America, the
Company incurred $8.6 million, $11.6 million, and $8.9 million in incremental research and development costs during the
years ended December 31, 2024, 2023, and 2022, respectively, to reflect the obligations of each party under the collaboration
to bear 50% of the development costs incurred.
The Company and AbbVie began commercializing LINZESS in the U.S. in December 2012. The Company receives
50% of the net profits and bears 50% of the net losses from the commercial sale of LINZESS in the U.S. Net profits or net
losses consist of net sales of LINZESS to third-party customers and sublicense income in the U.S. less the cost of goods sold
as well as selling, general and administrative expenses. LINZESS net sales are calculated and recorded by AbbVie and may
include gross sales net of discounts, rebates, allowances, sales taxes, freight and insurance charges, and other applicable
deductions.
The Company evaluated its linaclotide collaboration arrangement for North America and concluded that all
development-period performance obligations had been satisfied as of September 2012. The Company has determined that
there are three remaining commercial-period performance obligations, which include the sales detailing of LINZESS,
participation in the joint commercialization committee, and approved additional trials. The consideration remaining includes
cost reimbursements in the U.S. and net profit and loss sharing payments based on net sales in the U.S. Additionally, the
Company receives royalties in the mid-teens percent based on net sales in Canada and Mexico. Royalties and net profit and
loss sharing payments will be recorded as collaborative arrangements revenue or expense in the period earned, as these
payments relate predominately to the license granted to AbbVie. The Company records royalty revenue in the period earned
based on royalty reports from its partner, if available, or based on the projected sales and historical trends. The cost
reimbursements received from AbbVie during the commercialization period will be recognized as earned in accordance with
the right-to-invoice practical expedient, as the Company’s right to consideration corresponds directly with the value of the
services transferred during the commercialization period.
Under the Company’s linaclotide collaboration agreement for North America, LINZESS net sales are calculated and
recorded by AbbVie and include gross sales net of discounts, rebates, allowances, sales taxes, freight and insurance charges,
and other applicable deductions, as noted above. These amounts include the use of estimates and judgments, which could be
adjusted based on actual results in the future. The Company records its share of the net profits or net losses from the sales of
LINZESS in the U.S. less commercial expenses on a net basis, and presents the settlement payments to and from AbbVie as
collaboration expense or collaborative arrangements revenue, as applicable. This treatment is in accordance with the
Company’s revenue recognition policy, given that the Company is not the primary obligor and does not have the inventory
risks in the collaboration agreement with AbbVie for North America. The Company relies on AbbVie to provide accurate and
complete information related to net sales of LINZESS in accordance with U.S. generally accepted accounting principles in
order to calculate its settlement payments to and from AbbVie and record collaboration expense or collaborative arrangements
revenue, as applicable.
During the year ended December 31, 2024, the Company recognized 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. Excluding the changes in estimates, net income per share – basic and net income per share – diluted would have been
$0.21 and $0.19, respectively, for the year ended December 31, 2024.
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F-24
The following table summarizes collaborative arrangements revenue from the linaclotide collaboration agreement for
North America during the years ended December 31, 2024, 2023, and 2022 as follows (in thousands):
Year Ended December 31,
2024
2023
2022
Collaborative arrangements revenue related to sales of LINZESS in the U.S.
$
340,394
$
430,463
$
398,767
Royalty revenue
2,760
2,779
2,731
Total collaborative arrangements revenue
$
343,154
$
433,242
$
401,498
The Company incurred $39.3 million, $37.1 million, and $34.3 million in total selling, general and administrative
costs related to the sale of LINZESS in the U.S. in accordance with the cost-sharing arrangement with AbbVie for the years
ended December 31, 2024, 2023, and 2022, respectively.
In May 2014, CONSTELLA® became commercially available in Canada and, in June 2014, LINZESS became
commercially available in Mexico. The Company records royalties on sales of CONSTELLA in Canada and LINZESS in
Mexico in the period earned. The Company recognized $2.8 million, $2.8 million, and $2.7 million of combined royalty
revenues from Canada and Mexico during the years ended December 31, 2024, 2023, and 2022, respectively.
License Agreement with AbbVie (All countries other than the countries and territories of North America, China (including
Hong Kong and Macau), and Japan)
The Company has a license agreement with AbbVie to develop, manufacture and commercialize linaclotide in (i)
Europe, and (ii) all other countries other than China (including Hong Kong and Macau), Japan, and the countries and
territories of North America, or collectively the “Expanded Territory”, for the treatment of IBS-C, CIC and other GI
conditions.
Under the license agreement, as amended, AbbVie is obligated to pay the Company, (i) royalties based on sales
volume in Europe in the upper-teens percent, and (ii) on a country-by-country and product-by-product basis in the Expanded
Territory, a royalty as a percentage of net sales of products containing linaclotide as an active ingredient in the upper-single
digits for five years following the first commercial sale of a linaclotide product in a country, and in the low-double digits
thereafter. The royalty rate for products in Europe and the Expanded Territory will decrease, on a country-by-country basis, to
the lower-single digits, or cease entirely, following the occurrence of certain events. The license agreement also contains
certain sales-based milestones and commercial launch milestones, which could total up to $42.5 million.
The Company recognized $3.2 million, $2.8 million and $2.4 million of royalty revenue during the years ended
December 31, 2024, 2023, and 2022, respectively.
License Agreement for Japan with Astellas
The Company has a license agreement with Astellas to develop, manufacture, and commercialize linaclotide for the
treatment of IBS-C, CIC and other GI conditions in Japan.
Under the license agreement, as amended, Astellas is required to pay royalties to the Company at rates beginning in
the mid-single digit percent and escalating to low-double-digit percent, based on aggregate annual net sales in Japan of
products containing linaclotide as an active ingredient. These royalty payments are subject to reduction following the
expiration of certain licensed patents and the occurrence of generic competition in Japan.
During the years ended December 31, 2024, 2023, and 2022, the Company recognized $1.7 million, $1.8 million and
$2.0 million of royalty revenue, respectively.
Collaboration Agreement for China (including Hong Kong and Macau) with AstraZeneca
The Company has a collaboration agreement with AstraZeneca under which AstraZeneca has the exclusive right to
develop, manufacture and commercialize products containing linaclotide in the AstraZeneca License Territory.
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F-25
Under the collaboration agreement, AstraZeneca is required to pay tiered royalties to the Company at rates beginning
in the mid-single-digit percent and increasing up to twenty percent based on the aggregate annual net sales of products
containing linaclotide in the AstraZeneca License Territory. In addition, AstraZeneca may be required to make milestone
payments totaling up to $90.0 million contingent on the achievement of certain sales targets.
During the years ended December 31, 2024, 2023, and 2022, the Company recognized $0.4 million, $0.4 million and
$0.6 million of royalty revenue, respectively.
At December 31, 2023, the Company had accounts receivable in the amount of $15.0 million related to the third and
final installment of a non-contingent receivable due from AstraZeneca in connection with an amendment to the collaboration
agreement executed during 2019. The non-contingent receivable was collected in full during the first quarter of 2024.
Apraglutide Agreements
Development and Commercialization Agreement with AKP
In March 2022, VectivBio entered into a development and commercialization agreement with Asahi Kasei Pharma
Corporation (“AKP”) in which VectivBio granted an exclusive license to AKP, with the right to sublicense in multiple tiers, to
develop, commercialize and exploit products derived from apraglutide in Japan.
Pursuant to the terms of the development and commercialization agreement with AKP, VectivBio received an upfront
payment of JPY 3,000 million ($24.6 million at date of agreement) and development-related payments of JPY 1,600 million in
the aggregate ($13.1 million at date of agreement), and is eligible to receive development milestones of JPY 1,000 million
($8.2 million at date of agreement) and up to JPY 19,000 million ($155.8 million at date of agreement) of commercial and
sales-based milestone payments. VectivBio is also eligible to receive payments in the commercial period for manufacturing
supply equal to cost-plus manufacturing mark-up and tiered royalties of up to a mid-double-digit percentage on product sales
continuing until the later of (i) expiration of regulatory exclusivity in Japan, or (ii) expiration of the last valid patent claim that
provides exclusivity to apraglutide in Japan (the “Royalty Term”). The development and commercialization agreement will
terminate upon the expiration of the Royalty Term.
The Company identified two performance obligations consisting of the (i) exclusive license for the development and
commercialization of apraglutide in Japan and (ii) development activities for conducting global trials and sharing of associated
development data necessary for obtaining and maintaining regulatory approval in Japan. Each performance obligation was
capable of being distinct and distinct in the context of the contract. The initial transaction price was allocated to each
performance obligation on a relative standalone selling price basis. The Company assessed that it provided a right to use the
license as the license exists (in terms of form and functionality) at the point in time at which it is granted and therefore, was
satisfied at the inception of the arrangement. The development activities are being recognized over time as the Company
performs development activities related to the global trials. The Company recognizes revenue associated with the development
activities using an input method, according to the costs incurred, which in management’s judgment, is the best measure of
progress towards satisfying the performance obligation. Under the sales-or-usage-based royalty exception, revenue related to
sales-based milestone payments and royalty payments will be recognized as the underlying sales occur.
Prior to the VectivBio Acquisition, VectivBio had received the upfront payment of JPY 3,000 million ($24.6 million
at date of agreement), development-related payments of JPY 1,100 million ($9.0 million at date of agreement), and
development milestones of JPY 500 million ($4.1 million at date of agreement). Upon the acquisition of VectivBio on June 29,
2023, the Company assumed a contract liability for deferred revenue related to the development-related payments at its fair
value of $4.3 million.
In April 2024, VectivBio received the final development-related payment of JPY 500 million ($4.1 million at date of
agreement).
The Company recognized $2.2 million of revenue during the year ended December 31, 2024. The Company
recognized $2.0 million of revenue during the period between the acquisition date of June 29, 2023 and December 31, 2023
related to development activities. As of December 31, 2024, current deferred revenue of $2.0 million and non-current deferred
revenue of $1.8 million is reported within accrued expenses and other current liabilities and other
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F-26
liabilities, respectively, on the consolidated balance sheets. Deferred revenue and future payments received related to
development activities are expected to be recognized over the course of the development activities, which are expected to
occur through 2028.
License Agreement with Ferring
In August 2012, as subsequently amended and restated in December 2016, GlyPharma entered into an exclusive
licensing agreement with Ferring International Center, S.A. (“Ferring”), pursuant to which Ferring granted GlyPharma an
exclusive, worldwide, sublicensable license under certain patent rights and know-how controlled by Ferring relating to
apraglutide and certain know-how controlled by Ferring relating to specified alternate drug compounds, to research, develop,
manufacture, make, have made, import, export, use, sell, distribute, promote, advertise, dispose of or offer to sell (i) products
containing apraglutide whose manufacture, use or sale is covered by a valid claim of the licensed patents, or licensed products
and (ii) products, containing a specified alternate drug compound, or alternate drug products. In April 2021, the license
agreement was transferred and assigned to VectivBio AG, a subsidiary of VectivBio.
Under the license agreement, as partial consideration for the rights Ferring granted to it, VectivBio AG is required to
pay Ferring a high single-digit percentage royalty on worldwide annual net sales of licensed products and alternate drug
products until, on a country-by-country basis and licensed product-by-licensed product or alternate drug product-by-alternate
drug product basis, as applicable, the date on which the manufacture, use or sale of such licensed product or alternate drug
product, as applicable, ceases to be covered by a valid claim of a patent within the licensed patents in such a country.
GlyPharma was also required to issue Ferring a certain number of warrants and Class A preferred shares pursuant to a
shareholders’ agreement. The equity obligations under the license agreement have been fully performed by GlyPharma.
The Company is also obligated to pay Ferring a specified percentage of the annual consideration VectivBio AG or its
affiliates, including the Company, received in connection with sales of licensed product or alternate drug product by any third
parties to which VectivBio AG or its affiliates, including the Company, grant a sublicense of any of the rights licensed to
VectivBio AG by Ferring under this license agreement. Such percentage is in the high single digits for sales of both licensed
products and alternate drug products, and such payments are owed for the duration of the royalty term for licensed products or
alternate drug products, as applicable.
Other Collaboration and License Agreements
Collaboration and License Option Agreement with COUR
In November 2021, the Company entered into the COUR Collaboration Agreement, pursuant to which the Company
was granted an option (the “Option”) to acquire an exclusive license to research, develop, manufacture and commercialize, in
the U.S., products containing CNP-104 for the treatment of PBC. COUR has initiated a Phase II clinical study to evaluate the
safety, tolerability, and pharmacodynamic effects and efficacy of CNP-104 in PBC patients. After reviewing the data from the
clinical study for CNP-104, the Company had the right to exercise the Option and pay COUR $35.0 million in exchange for
the license, subject to the Company’s right to apply a credit against such payment as described below.
In April 2023, the Company and COUR executed an amendment to the COUR Collaboration Agreement, in which
the Company agreed to pay a one-time, non-refundable, upfront payment of $6.0 million to COUR in exchange for the right to
apply a credit of $6.6 million against future amounts due to COUR in connection with the exercise of the Option, commercial
milestones, or royalties. In connection with such payment, COUR also granted the Company a right of first negotiation over
certain additional potential research and development programs. The $6.0 million payment was
recognized as research and development expense in the second quarter of 2023.
In the third quarter of 2024, the Company received from COUR the topline data from COUR’s Phase II clinical study
for the treatment of PBC. In September 2024, the Company notified COUR of its decision not to exercise the option to acquire
an exclusive license to CNP-104. As a result, the collaboration and license option agreement between the Company and
COUR has terminated, and the Company retains no rights and has no obligations related to CNP-104.
Other Agreements
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F-27
Disease Education and Promotional Agreement with Alnylam
In August 2019, the Company and Alnylam Pharmaceuticals, Inc. (“Alnylam”) entered into a disease education and
promotional agreement (the “Alnylam Agreement”) for Alnylam’s GIVLAARI (givosiran) for the treatment of acute hepatic
porphyria. The Alnylam Agreement, as amended, was terminated in June 2021 with an effective termination date of September
30, 2021. Under the terms of the Alnylam Agreement, the Company’s sales force performed disease awareness activities and
sales detailing activities for GIVLAARI. The Company remained eligible to receive royalties based on a percentage of net
sales of GIVLAARI that are directly attributable to the Company’s promotional efforts through September 30, 2022, which
was one year following the termination of the agreement.
During the year ended December 31, 2022 the Company recognized $2.2 million in royalty revenue.
6. Fair Value of Financial Instruments
The tables below present information about the Company’s assets and liabilities that are measured at fair value on a
recurring basis as of December 31, 2024 and 2023 and indicate the fair value hierarchy of the valuation techniques the
Company utilized to determine such fair value. In general, fair values determined by Level 1 inputs utilize observable inputs
such as quoted prices in active markets for identical assets or liabilities. Fair values determined by Level 2 inputs utilize data
points that are either directly or indirectly observable, such as quoted prices for similar instruments in active markets, interest
rates and yield curves. Fair values determined by Level 3 inputs utilize unobservable data points in which there is little or no
market data, which require the Company to develop its own assumptions for the asset or liability.
The Company’s investment portfolio may include fixed income securities that do not always trade on a daily basis.
As a result, the pricing services used by the Company apply other available information as applicable through processes such
as benchmark yields, benchmarking of like securities, sector groupings and matrix pricing to prepare valuations. In addition,
model processes are used to assess interest rate impact and develop prepayment scenarios. These models take into
consideration relevant credit information, perceived market movements, sector news and economic events. The inputs into
these models may include benchmark yields, reported trades, broker-dealer quotes, issuer spreads and other relevant data. The
Company validates the prices provided by its third party pricing services by obtaining market values from other pricing
sources and analyzing pricing data in certain instances. The Company periodically invests in certain reverse repurchase
agreements, which are collateralized by Government Securities and Obligations for an amount not less than 102% of their
principal amount. The Company does not record an asset or liability for the collateral as the Company is not permitted to sell
or re-pledge the collateral. The collateral has at least the prevailing credit rating of U.S. Government Treasuries and Agencies.
The Company utilizes a third-party custodian to manage the exchange of funds and ensure the collateral received is
maintained at 102% of the reverse repurchase agreements principal amount on a daily basis.
The following tables present the assets the Company has measured at fair value on a recurring basis (in thousands):
Fair Value Measurements at Reporting Date Using
Quoted Prices in Significant Other
Significant
Active Markets for
Observable
Unobservable
December 31,
Identical Assets
Inputs
Inputs
2024
(Level 1)
(Level 2)
(Level 3)
Assets:
Cash and cash equivalents:
Money market funds
$
36,010 $
36,010
$
—
$
—
U.S. Treasury securities
11,044
—
11,044
—
Commercial paper
7,928
—
7,928
—
Total assets measured at fair value
$
54,982 $
36,010
$
18,972
$
—
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F-28
Fair Value Measurements at Reporting Date Using
Quoted Prices in Significant Other
Significant
Active Markets for
Observable
Unobservable
December 31,
Identical Assets
Inputs
Inputs
2023
(Level 1)
(Level 2)
(Level 3)
Assets:
Cash and cash equivalents:
Money market funds
$
45,939 $
45,939
$
—
$
—
U.S. Treasury securities
10,507
—
10,507
—
Commercial paper
2,240
—
2,240
—
Total assets measured at fair value
$
58,686 $
45,939
$
12,747
$
—
Cash equivalents, accounts receivable, prepaid expenses and other current assets, accounts payable, accrued research
and development costs, accrued expenses and other current liabilities and current portion of operating lease obligations at
December 31, 2024 and 2023 are carried at amounts that approximate fair value due to their short-term maturities.
Convertible Senior Notes
In August 2019, the Company issued $200.0 million aggregate principal amount of its 0.75% convertible senior notes
due 2024 (the “2024 Convertible Notes”) and $200.0 million aggregate principal amount of its 1.50% convertible senior notes
due 2026 (the “2026 Convertible Notes”) (Note 10). The fair value of the respective convertible senior notes, which differs
from their carrying value, is influenced by interest rates, the price of the Company’s Class A Common Stock and the volatility
thereof, and the prices for the respective convertible senior notes observed in market trading, which are Level 2 inputs.
In June 2024, the Company repaid the aggregate principal amount of the 2024 Convertible Notes upon maturity
(Note 10). The estimated fair value of the 2024 Convertible Notes was $209.6 million as of December 31, 2023. The estimated
fair value of the 2026 Convertible Notes was $186.6 million and $217.1 million as of December 31, 2024 and 2023,
respectively.
Capped Calls with Respect to 2024 Convertible Notes and 2026 Convertible Notes
In connection with the issuance of the 2024 Convertible Notes and the 2026 Convertible Notes, the Company entered
into the Capped Calls with certain financial institutions. The Capped Calls cover 29,867,480 shares of Class A Common Stock
(subject to anti-dilution and certain other adjustments), which is the same number of shares of Class A Common Stock that
initially underlie the 2024 Convertible Notes and the 2026 Convertible Notes. The Capped Calls have an initial strike price of
approximately $13.39 per share, which corresponds to the initial conversion price of the 2024 Convertible Notes and the 2026
Convertible Notes, and have a cap price of approximately $17.05 per share (Note 10). The strike price and cap price are
subject to anti-dilution adjustments generally similar to those applicable to the 2024 Convertible Notes and the 2026
Convertible Notes. These instruments meet the conditions outlined in ASC 815, to be classified in stockholders’ equity and are
not subsequently remeasured as long as the conditions for equity classification continue to be met (Note 10).
Revolving Credit Agreement
Outstanding borrowings under the revolving credit facility (Note 10) are carried at amounts that approximate fair
value based on their nature, terms, credit spreads, and variable interest rates, which are Level 3 inputs.
Non-recurring Fair Value Measurements
Acquired IPR&D
The fair value of the acquired IPR&D asset, apraglutide, was determined using the multi-period excess earnings
method using Level 3 fair value measurements and inputs including estimated cash flows and probabilities of success.
Assembled Workforce
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F-29
The fair value of the assembled workforce was determined using the replacement cost method using Level 3 fair
value measurements and inputs including estimated costs and productivity metrics.
7. Leases
The Company’s lease portfolio for the year ended December 31, 2024 included: an office lease for its current
headquarters location and other locations, vehicle leases for its salesforce representatives, and leases for computer and office
equipment.
The Company’s headquarters office lease and vehicle leases require letters of credit totaling $1.2 million to secure the
Company’s obligations under the lease agreements. The letters of credit are maintained under a subfacility of the revolving
credit agreement (Note 10).
Lease cost is recognized on a straight-line basis over the lease term. The components of lease cost for the years ended
December 31, 2024, 2023, and 2022 are as follows (in thousands):
Year Ended December 31,
2024
2023
2022
Operating lease cost
$ 2,507
$ 2,507
$ 2,509
Short-term lease cost
1,520
1,241
1,070
Total lease cost
$ 4,027
$ 3,748
$ 3,579
Supplemental information related to leases for the periods reported is as follows:
Year Ended December 31,
2024
2023
2022
Cash paid for amounts included in the measurement of lease liabilities (in
thousands)
$
3,126
$ 3,065
$ 3,114
Weighted-average remaining lease term of operating leases (in years)
5.4
6.4
7.3
Weighted-average discount rate of operating leases
5.8 %
5.8 %
5.8 %
Summer Street Lease
In June 2019, the Company entered into a non-cancelable operating lease (the “Summer Street Lease”) for
approximately 39,000 square feet of office space on the 23rd floor of 100 Summer Street, Boston, Massachusetts, which has
been the Company’s headquarters since October 2019. The Summer Street Lease terminates on June 11, 2030 and includes a
2% annual rent escalation, free rent periods, a tenant improvement allowance, and an option to extend the term of the lease for
an additional five years at a market base rental rate. The extension option is not included in the lease term used for the
measurement of the lease, as it is not reasonably certain to be exercised. The lease expense, inclusive of the escalating rent
payments and lease incentives, is recognized on a straight-line basis over the lease term.
At lease commencement, the Company recorded a right-of-use asset and a lease liability using an incremental
borrowing rate of 5.8%. At December 31, 2024, the balances of the right-of-use asset and operating lease liability were $11.0
million and $15.5 million, respectively. At December 31, 2023, the balances of the right-of-use asset and operating lease
liability were $12.6 million and $17.7 million, respectively.
Lease costs recorded during each of the years ended December 31, 2024, 2023, and 2022 were $2.5 million.
Future minimum lease payments under the Summer Street Lease as of December 31, 2024 are as follows (in
thousands):
2025
$
3,189
2026
3,252
2027
3,317
2028
3,384
2029 and thereafter
4,902
Total future minimum lease payments
18,044
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F-30
Less: present value adjustment
(2,551)
Operating lease liabilities
15,493
Less: current portion of operating lease liabilities
(3,189)
Operating lease liabilities, net of current portion
$
12,304
8. Property and Equipment
Property and equipment, net consisted of the following (in thousands):
December 31,
2024
2023
Software
$
1,567
$
1,652
Leasehold improvements
7,407
7,407
Laboratory equipment
—
1,327
Furniture and fixtures
1,732
1,747
Computer and office equipment
2,154
2,341
12,860
14,474
Less accumulated depreciation and amortization
(8,365)
(8,889)
$
4,495
$
5,585
Depreciation expense of property and equipment was $1.2 million, $1.2 million and $1.4 million for the years ended
December 31, 2024, 2023, and 2022, respectively.
9. Accrued Expenses and Other Current Liabilities
Accrued expenses and other current liabilities consisted of the following (in thousands):
December 31, 2024
December 31, 2023
Accrued compensation and benefits
$
14,547
$
19,937
Accrued interest
4,771
5,953
Deferred revenue
2,032
2,620
Accrued restructuring liabilities
560
8,303
Accrued taxes
521
1,244
Other
4,418
6,197
Total accrued expenses and other current liabilities
$
26,849
$
44,254
As of December 31, 2024 and 2023, other accrued expenses were comprised primarily of $4.3 million and $6.1
million of uninvoiced vendor liabilities, respectively.
10. Debt
2.25% Convertible Senior Notes due 2022
In June 2015, the Company issued $335.7 million aggregate principal amount of the 2022 Convertible Notes. The
Company received net proceeds of $324.0 million from the sale of the 2022 Convertible Notes, after deducting fees and
expenses of $11.7 million. The Company used $21.1 million of the net proceeds from the sale of the 2022 Convertible Notes
to pay the net cost of the Convertible Note Hedges (after such cost was partially offset by the proceeds to the Company from
the sale of the Note Hedge Warrants), as described below.
In connection with the issuance of the 2024 Convertible Notes and the 2026 Convertible Notes in August 2019, the
Company repurchased $215.0 million aggregate principal amount of the 2022 Convertible Notes. Such portion of the 2022
Convertible Notes were repurchased at a premium totaling $227.3 million.
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F-31
In June 2022, the Company repaid the remaining $120.7 million aggregate principal amount of the 2022 Convertible
Notes upon maturity.
The 2022 Convertible Notes were governed by an indenture (the “2022 Indenture”) between the Company and U.S.
Bank National Association, as trustee (the “Trustee”). The 2022 Convertible Notes were senior unsecured obligations and bore
cash interest at the annual rate of 2.25%, payable on June 15 and December 15 of each year. The 2022 Convertible Notes
matured on June 15, 2022. No conversions were exercised by holders of the 2022 Convertible Notes.
0.75% Convertible Senior Notes due 2024 and 1.50% Convertible Senior Notes due 2026
In August 2019, the Company issued $200.0 million aggregate principal amount of the 2024 Convertible Notes and
$200.0 million aggregate principal amount of the 2026 Convertible Notes, pursuant to separate indentures (each an
“Indenture” and together the “Indentures”), between the Company and U.S. Bank National Association, as trustee (the
“Trustee”). The Company received net proceeds of $391.0 million from the sale of the 2024 Convertible Notes and 2026
Convertible Notes, after deducting fees and expenses of $9.0 million. The Company used $25.2 million of the net proceeds
from the sale of the 2024 Convertible Notes and 2026 Convertible Notes to pay the cost of the Capped Calls, as described
below.
In June 2024, the Company repaid the $200.0 million aggregate principal amount of the 2024 Convertible Notes
upon maturity. The 2024 Convertible Notes bore cash interest at the annual rate of 0.75% payable on June 15 and December
15 of each year. No conversions were exercised by holders of the 2024 Convertible Notes.
The 2026 Convertible Notes bear cash interest at the annual rate of 1.50%, payable on June 15 and December 15 of
each year. The 2026 Convertible Notes will mature on June 15, 2026, unless earlier converted or repurchased.
The initial conversion rate for the 2026 Convertible Notes is 74.6687 shares of Class A Common Stock (subject to
adjustment as provided for in the Indenture) per $1,000 principal amount of the 2026 Convertible Notes, which is equal to an
initial conversion price of approximately $13.39 per share.
The Company will settle conversions of the 2026 Convertible Notes through payment or delivery, as the case may be,
of cash, shares of the Company’s Class A Common Stock or a combination of cash and shares of Class A Common Stock, at
the Company’s option (subject to, and in accordance with, the settlement provisions of the Indenture).
Holders of the 2026 Convertible Notes may convert their notes at their option at any time prior to the close of
business on the business day immediately preceding December 15, 2025 in multiples of $1,000 principal amount, only under
the following circumstances:
●
during any calendar quarter commencing after the calendar quarter ending on December 31, 2019 (and only
during such calendar quarter), if the last reported sale price of Class A Common Stock for at least 20 trading
days (whether or not consecutive) during a period of 30 consecutive trading days ending on the last trading day
of the immediately preceding calendar quarter is greater than or equal to 130% of the conversion price for the
2026 Convertible Notes on each applicable trading day;
●
during the five-business day period after any five consecutive trading day period (the “measurement period”) in
which the “trading price” (as defined in each Indenture) per $1,000 principal amount of the 2026 Convertible
Notes for each trading day of the measurement period was less than 98% of the product of the last reported sale
price of Class A Common Stock and the conversion rate for the 2026 Convertible Notes on each such trading
day; or
●
upon the occurrence of specified corporate events described in the Indenture.
On or after December 15, 2025 until the close of business on the second scheduled trading day immediately
preceding the applicable June 15, 2026, the holders of the 2026 Convertible Notes may convert their 2026 Convertible Notes,
in multiples of $1,000 principal amount, regardless of the foregoing conditions.
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F-32
Upon the occurrence of fundamental changes, as described in the Indenture, prior to the maturity date of the 2026
Convertible Notes, holders of such notes may require the Company to repurchase for cash all or a portion of their notes at a
repurchase price equal to 100% of the principal amount of the notes to be repurchased, plus accrued and unpaid interest. If a
make-whole fundamental change, as described in the Indenture, occurs and a holder elects to convert its notes in connection
with such make-whole fundamental change, such holder may be entitled to an increase in the conversion rate as described in
the Indenture.
The Indenture does not contain any financial covenants or restrict the Company’s ability to repurchase the
Company’s securities, pay dividends or make restricted payments in the event of a transaction that substantially increases the
Company’s level of indebtedness. The Indenture provides for customary events of default. In the case of an event of default
arising from specified events of bankruptcy or insolvency, all outstanding notes will become due and payable immediately
without further action or notice. If any other event of default under the Indenture occurs or is continuing, the Trustee or
holders of at least 25% in aggregate principal amount of the then outstanding notes may declare the principal amount of such
notes to be immediately due and payable.
The Company accounts for convertible debt instruments as a single liability measured at amortized cost.
The Company’s outstanding balances for the convertible senior notes consisted of the following (in thousands):
2024
2023
Principal:
2024 Convertible Notes
$
—
$ 200,000
2026 Convertible Notes
200,000
200,000
Less: unamortized debt issuance costs
(1,012)
(2,131)
Net carrying amount
$ 198,988
$ 397,869
In connection with the issuance of the 2024 Convertible Notes and the 2026 Convertible Notes, the Company
incurred $9.0 million of debt issuance costs, which primarily consisted of initial purchaser’s discounts and legal and other
professional fees. The debt issuance costs are reflected as a reduction in the carrying value of the convertible senior notes and
recorded as interest expense over the life of the 2024 Convertible Notes and the 2026 Convertible Notes.
The Company determined the expected life of the 2024 Convertible Notes and the 2026 Convertible Notes was equal
to their approximately five and seven-year terms, respectively. The effective annual interest rate of the 2024 Convertible Notes
for the period from the date of issuance through maturity was 1.2%. The effective annual interest rate of the 2026 Convertible
Notes for the period from the date of issuance through December 31, 2024 was 1.9%. The effective annual interest rate is
computed using the contractual interest and the amortization of debt issuance costs.
The following table sets forth total interest expense recognized related to convertible senior notes (in thousands):
Year Ended December 31,
2024
2023
2022
Contractual interest expense
$
3,688
$
4,500
$
5,745
Amortization of debt issuance costs
1,119
1,618
1,853
Total interest expense
$
4,807
$
6,118
$
7,598
Future minimum payments under the convertible senior notes as of December 31, 2024, are as follows (in
thousands):
2025
$
3,000
2026
201,500
Total future minimum payments under the convertible senior notes
204,500
Less: amounts representing interest
(4,500)
Less: unamortized debt issuance costs
(1,012)
Convertible senior notes balance
$
198,988
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F-33
Capped Calls with Respect to 2024 Convertible Notes and 2026 Convertible Notes
To minimize the impact of potential dilution to the Company’s Class A common stockholders upon conversion of the
2024 Convertible Notes and the 2026 Convertible Notes, the Company separately entered into the capped call transactions in
August 2019 (the “Capped Calls”) in connection with the issuance of the 2024 Convertible Notes and the 2026 Convertible
Notes. The Company paid the counterparties $25.2 million to enter into the Capped Calls, of which $25.0 million related to
the premium payments and $0.2 million related to transaction costs. These instruments meet the conditions outlined in ASC
815 to be classified in stockholders’ equity and are not subsequently remeasured as long as the conditions for equity
classification continue to be met.
The Capped Calls in connection with the issuance of the 2024 Convertible Notes, which covered 14,933,740 shares
of Class A Common Stock, terminated unexercised upon expiry in June 2024.
The Capped Calls in connection with the 2026 Convertible Notes have an initial strike price of approximately $13.39
per share, which corresponds to the initial conversion price of the 2026 Convertible Notes and is subject to anti-dilution
adjustments generally similar to those applicable to the 2026 Convertible Notes. The Capped Calls have a cap price of
approximately $17.05 per share, subject to certain adjustments. The Capped Calls cover 14,933,740 shares of Class A
Common Stock (subject to anti-dilution and certain other adjustments), which is the same number of shares of Class A
Common Stock that initially underlie the 2026 Convertible Notes. Holders of the 2026 Convertible Notes do not have any
rights with respect to the Capped Calls.
The Capped Calls are expected generally to reduce the potential dilution to the Class A Common Stock upon
conversion of the 2026 Convertible Notes in the event that the market price per share of Class A Common Stock is greater
than the strike price of the Capped Calls as adjusted pursuant to the anti-dilution adjustments. If, however, the market price
per share of Class A Common Stock exceeds the cap price of the Capped Calls, there would nevertheless be dilution upon
conversion of the 2026 Convertible Notes to the extent that such market price exceeds the cap price of the Capped Calls.
Revolving Credit Facility
In May 2023, in connection with the VectivBio Acquisition, the Company entered into a credit agreement with Wells
Fargo Bank, N.A., as administrative agent (in such capacity, the “Agent”), collateral agent, a letter of credit issuer and a
lender, and the other agents, lenders and letter of credit issuers parties thereto (collectively, the “Lenders”). In September
2024, the Company, the Agent and the Lenders entered into the first amendment to the revolving credit agreement (as
amended from time to time, the “Revolving Credit Agreement”) to, among other things, increase the quantum of the
Revolving Credit Facility from $500.0 million to $550.0 million, extend the maturity date, and increase the Company’s
permitted maximum consolidated secured net leverage ratio.
The Revolving Credit Agreement provides for a $550.0 million secured revolving credit facility (the "Revolving
Credit Facility”), which includes a $10.0 million letter of credit subfacility, and loans made thereunder will mature on the
earliest to occur of (i) December 31, 2028 or (ii) the date that is 91 days prior to the stated maturity date of the Company’s
existing convertible notes then outstanding, unless, in the case of clause (ii), the Company’s minimum liquidity equals or
exceeds certain agreed levels.
At the Company’s election, borrowings under the Revolving Credit Agreement will bear interest at a rate equal to (a)
Adjusted Term Secured Overnight Financing Rate (“Adjusted Term SOFR”) (as defined in Revolving Credit Agreement) plus
the applicable rate (ranging from 1.75% to 3.00%) or (b) the highest of (1) the weighted average overnight Federal funds rate,
as published by the Federal Reserve Bank of New York, plus one half of 1.0%, (2) the prime lending rate or (3) the one-month
Adjusted Term SOFR plus 1.0% in effect from time to time plus the applicable rate (ranging from 0.75% to 2.00%). The
applicable rates are based on the Company’s consolidated secured net leverage ratio (as defined under the Revolving Credit
Facility) at the time of the applicable borrowing.
The Company pays a quarterly commitment fee of 0.30% to 0.425% on the daily amount by which the commitments
under the Revolving Credit Agreement exceed the outstanding loans and letters of credit.
The loans and other obligations under the Revolving Credit Agreement are secured by substantially all of the
Company’s personal property, including a pledge of all the capital stock of subsidiaries held directly by the Company or
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F-34
any subsidiary that guarantees the Revolving Credit Agreement following the closing date (which pledge, in the case of any
foreign subsidiary, is limited to 65% of the voting stock), subject to certain customary exceptions and limitations. The
Revolving Credit Agreement generally prohibits any other liens on the assets of the Company and its restricted subsidiaries,
subject to certain exceptions as described in the Revolving Credit Agreement.
Under the terms of the Revolving Credit Agreement, the Company will be able to request an increase in the
commitments or the addition of a term loan secured by a pari passu lien on the collateral of up to an additional amount equal
to the greater of $200.0 million and 100% of the trailing twelve-month Consolidated Adjusted EBITDA (as defined in the
Revolving Credit Agreement) upon satisfaction of customary conditions, including receipt of commitments from either new
lenders or increased commitments from existing lenders.
The Revolving Credit Agreement contains certain customary covenants applicable to the Company and its Restricted
Subsidiaries (as defined in the Revolving Credit Agreement). The Company is required to maintain a maximum consolidated
secured net leverage ratio of 3.50 to 1.00 until the end of the final quarter of 2025 (the “Initial Period”), (ii) 3.25 to 1.00 until
the end of the first quarter of 2026 (the “Interim Period”) and (iii) 3.00 to 1.00 thereafter, and a minimum interest coverage
ratio of 3.00 to 1.00, in each case at the end of each fiscal quarter. The Revolving Credit Agreement allows the Company to
elect to increase the permitted maximum consolidated secured net leverage ratio to (i) 4.00 to 1.00 during the Initial Period,
(ii) 3.75 to 1.00 during the Interim Period and (iii) 3.50 to 1.00 thereafter, in each case for up to four fiscal quarters in the
event it consummates an acquisition for consideration in excess of $50.0 million, subject to certain limitations on how often
this election can be made. As of December 31, 2024, the Company was in compliance with all covenants under the Revolving
Credit Agreement.
In connection with the initial execution of the Revolving Credit Agreement during the second quarter of 2023 and the
amendment executed in the third quarter of 2024, the Company incurred $2.9 million and $2.2 million of debt issuance costs,
respectively, which consisted primarily of lender fees. The debt issuance costs are classified as other assets and are amortized
on a straight-line basis over the term of the Revolving Credit Agreement. The Company had unamortized capitalized debt
issuance costs of $3.9 million and $2.4 million at December 31, 2024 and 2023, respectively.
The outstanding principal balance on the revolving credit facility was $385.0 million and $300.0 million as of
December 31, 2024 and 2023, respectively.
The following table sets forth total interest expense recognized related to Revolving Credit Agreement (in
thousands):
Year Ended December 31,
2024
2023
Contractual interest expense
$
27,643
$
14,718
Amortization of debt issuance costs
785
442
Other financing costs
50
101
Total interest expense
$
28,478
$
15,261
11. Commitments and Contingencies
Commitments with AbbVie
The Company and AbbVie are jointly obligated to make minimum purchases of linaclotide API for the territories
covered by the Company’s collaboration with AbbVie for North America. Currently, AbbVie fulfills all such minimum
purchase commitments.
Under the collaboration agreement with AbbVie for North America, the Company shares all development and
commercialization costs related to linaclotide in the U.S. with AbbVie. The actual amounts that the Company pays to AbbVie
or that AbbVie pays to the Company will depend on numerous factors outside of the Company’s control, including the success
of certain clinical development efforts with respect to linaclotide, the content and timing of decisions made by the regulators,
the reimbursement and competitive landscape around linaclotide and the Company’s other product candidates, and other
factors.
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F-35
Other Funding Commitments
As of December 31, 2024, the Company has ongoing studies in various pre-clinical and clinical trial stages. The
Company’s most significant clinical trial expenditures are to contract research organizations. These contracts are generally
cancellable, with notice, at the Company’s option and do not have any significant cancellation penalties.
Guarantees
As permitted under Delaware law, the Company indemnifies its directors and certain of its officers for certain events
or occurrences while such director or officer is, or was, serving at the Company’s request in such capacity. The maximum
potential amount of future payments the Company could be required to make is unlimited; however, the Company has
directors’ and officers’ insurance coverage that is intended to limit its exposure and enable it to recover a portion of any future
amounts paid.
The Company enters into certain agreements with other parties in the ordinary course of business that contain
indemnification provisions. These typically include agreements with business partners, contractors, landlords, clinical sites
and customers. Under these provisions, the Company generally indemnifies and holds harmless the indemnified party for
losses suffered or incurred by the indemnified party as a result of the Company’s activities. These indemnification provisions
generally survive termination of the underlying agreements. The maximum potential amount of future payments the Company
could be required to make under these indemnification provisions is unlimited. However, to date the Company has not
incurred material costs to defend lawsuits or settle claims related to these indemnification provisions. As a result, the
estimated fair value of these obligations is minimal. Accordingly, the Company did not have any liabilities recorded for these
obligations as of December 31, 2024 and 2023.
Litigation
From time to time, the Company is involved in various legal proceedings and claims, either asserted or unasserted,
which arise in the ordinary course of business. While the outcome of these other claims cannot be predicted with certainty,
management does not believe that the outcome of any of these ongoing legal matters, individually and in aggregate, will have
a material adverse effect on the Company’s consolidated financial statements.
12. Stockholders’ Equity
Preferred Stock
The Company’s preferred stock may be issued from time to time in one or more series, with each such series to
consist of such number of shares and to have such terms as adopted by the board of directors. Authority is given to the board
of directors to determine and fix such voting powers, full or limited, or no voting powers, and such designations, preferences
and relative participating, optional or other special rights, and qualifications, limitation or restrictions thereof, including
without limitation, dividend rights, conversion rights, redemption privileges and liquidation preferences.
Common Stock
The Company has one class of common stock (“Class A Common Stock”). Class A Common Stock is entitled to one
vote per share. The Company has reserved, out of its authorized but unissued shares of Class A Common Stock, sufficient
shares to effect the conversion of the convertible senior notes and the Note Hedge Warrants pursuant to the terms thereof
(Note 10).
The Company’s stockholders are entitled to dividends if and when declared by the board of directors.
Share Repurchase Program
In May 2021, the Company’s Board of Directors authorized a program to repurchase up to $150.0 million of the
Company’s Class A Common Stock. The Company completed the share repurchase program in May 2022 and retired the
repurchased shares.
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F-36
During the year ended December 31, 2022, the Company repurchased 10.8 million shares of Class A Common Stock
at an aggregate cost of $123.4 million. For the overall program, under which repurchases commenced in December 2021, the
Company repurchased 13.1 million shares of Class A Common Stock at an average price per share of $11.47.
13. Employee Stock Benefit Plans
The Company has several share-based compensation plans under which stock options, RSAs, RSUs, and other share-
based awards are available for grant to employees, officers, directors and consultants of the Company.
The following table summarizes share-based compensation expense by award type (in thousands):
Year Ended December 31,
2024
2023
2022
Stock options
$
—
$
226
$
1,471
Time-based restricted stock units
21,425
19,829
17,643
Performance-based restricted stock units
6,422
9,321
5,008
Restricted stock awards
1,492
1,997
2,439
Employee stock purchase plan
451
502
412
Stock awards
60
130
75
VectivBio Holding AG stock options and RSUs accelerated upon change in control
—
27,548
—
Total share-based compensation expense
$ 29,850
$
59,553
$ 27,048
The following table summarizes the share-based compensation expense reflected in the consolidated statements of
income (in thousands):
Year Ended December 31,
2024
2023
2022
Share-based compensation expense:
Research and development
$
7,552
$ 17,448
$
4,936
Selling, general and administrative
22,298
41,194
22,112
Restructuring
—
911
—
Total share-based compensation expense included in operating expenses
29,850
59,553
27,048
Income tax benefit
3,414
2,964
1,644
Total share-based compensation expense, net of tax
$
26,436
$ 56,589
$ 25,404
In connection with the VectivBio Acquisition, the Company incurred $27.5 million of share-based compensation
expense during the second quarter of 2023 related to the vesting acceleration and settlement of outstanding VectivBio stock
options and RSUs under VectivBio’s 2021 Equity Incentive Plan, of which $11.3 million was recorded within research and
development expense and $16.2 million was recorded within selling, general and administrative expenses.
Restructuring expenses include modifications to share-based awards held by employees impacted by various
workforce reductions (Note 16).
Stock Benefit Plans
As of December 31, 2024, the Company has the following active stock benefit plans pursuant to which awards are
currently outstanding: the Amended and Restated 2019 Equity Incentive Plan (the “A&R 2019 Equity Plan”), the 2019 Equity
Incentive Plan (the “2019 Equity Plan”), the Amended and Restated 2010 Employee Stock Purchase Plan (the “2010 Purchase
Plan”) and the Amended and Restated 2010 Employee, Director, and Consultant Equity Incentive Plan (the “2010 Equity
Plan”). At December 31, 2024, there were 12,606,159 shares available for future grant under the A&R 2019 Equity Plan and
the 2010 Purchase Plan.
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F-37
A&R 2019 Equity Plan
During 2023, the Company’s stockholders approved the A&R 2019 Equity Plan under which stock options, RSAs,
RSUs, and other stock-based awards may be granted to employees, officers, directors, or consultants of the Company. Under
the A&R 2019 Equity Plan, 6,000,000 shares of Class A Common Stock were initially reserved for issuance. Subsequent to the
approval of the A&R 2019 Equity Plan, shares available for grant under the 2019 Equity Plan are made available for grant
under the A&R 2019 Equity Plan and awards that are returned to the A&R 2019 Equity Plan, 2019 Equity Plan and 2010
Equity Plan as a result of their expiration, cancellation, termination or repurchase are automatically made available for future
grant under the A&R 2019 Equity Plan. As of December 31, 2024, 8,523,616 shares were available for future grant under the
A&R 2019 Equity Plan.
2019 Equity Plan
During 2019, the Company’s stockholders approved the 2019 Equity Plan under which stock options, RSAs, RSUs,
and other stock-based awards may be granted to employees, officers, directors, or consultants of the Company. Under the 2019
Equity Plan, 10,000,000 shares of Class A Common Stock were initially reserved for issuance. Prior to the approval of the
A&R 2019 Equity Plan, awards that were returned to the 2010 Equity Plan as a result of their expiration, cancellation,
termination or repurchase were automatically made available for issuance under the 2019 Equity Plan and awards that expired,
cancelled, terminated, or were repurchased under the 2019 Equity Plan were no longer available for future grant. As of
December 31, 2024, there were no shares available for future grant under the 2019 Equity Plan.
2010 Purchase Plan
During 2010, the Company’s stockholders approved the 2010 Purchase Plan, which gives eligible employees the
right to purchase shares of common stock at the lower of 85% of the fair market value on the first or last day of an offering
period. Each offering period is six months. There were 400,000 shares of common stock initially reserved for issuance
pursuant to the 2010 Purchase Plan. The number of shares available for future grant under the 2010 Purchase Plan may be
increased on the first day of each fiscal year by an amount equal to the lesser of: (i) 1,000,000 shares, (ii) 1% of the Class A
shares of common stock outstanding on the last day of the immediately preceding fiscal year, or (iii) such lesser number of
shares as is determined by the board of directors. As of December 31, 2024, there were 4,082,543 shares available for future
grant under the 2010 Purchase Plan.
2010 Equity Plan
The 2010 Equity Plan provided for the granting of stock options, RSAs, RSUs, and other share-based awards to
employees, officers, directors, consultants, or advisors of the Company. As of December 31, 2024, there were no shares
available for future grant under the 2010 Equity Plan.
Restricted Stock Awards
RSAs are granted to non-employee members of the board of directors under restricted stock agreements in
accordance with the terms of the 2019 Equity Plan and the Company’s non-employee director compensation policy, effective
May 2019. Annual restricted stock grants to each non-employee member of the board of directors vest in full on the date
immediately preceding the next annual meeting of stockholders, provided the individual continues to serve on the Company’s
board of directors through each vest date. Initial restricted stock grants to new non-employee members of the board of
directors vest annually over a three-year period from the date of grant provided the individual continues to serve on the
Company’s board of directors through each vest date.
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F-38
A summary of restricted stock activity for the year ended December 31, 2024 is presented below:
Weighted-
Average
Number of
Grant Date
Shares
Fair Value
Unvested as of December 31, 2023
178,800
$
10.77
Granted
194,488
5.70
Vested
(178,800)
10.77
Forfeited
—
—
Unvested as of December 31, 2024
194,488
$
5.70
The weighted-average grant date fair value per share of RSAs granted during the years ended December 31, 2024,
2023, and 2022 was $5.70, $10.77, and $11.22, respectively. The total fair value of RSAs that vested during the years ended
December 31, 2024, 2023, and 2022 was $1.0 million, $2.1 million, and $2.8 million, respectively.
Restricted Stock Units
RSUs granted under the Company’s equity plans represent the right to receive one share of the Company’s Class A
Common Stock pursuant to the terms of the applicable award agreement. Shares of the Company’s Class A Common Stock are
delivered to the employee upon vesting, subject to payment of applicable withholding taxes.
Time-based RSUs
Time-based RSUs generally vest over a two-to-four-year period on the approximate anniversary of the date of grant
until fully vested, provided the individual remains in continuous service with the Company through each vesting date. The fair
value of all time-based RSUs is based on the market value of the Company's Class A Common Stock on the date of grant.
Compensation expense, including the effect of estimated forfeitures, is recognized over the applicable service period.
A summary of time-based RSU activity for the year ended December 31, 2024 is as follows:
Weighted-
Average
Number
Grant Date
of RSUs
Fair Value
Outstanding as of December 31, 2023
5,342,727
$
10.68
Granted
3,105,866
11.53
Vested and released
(1,886,372)
10.77
Forfeited
(1,210,714)
11.79
Outstanding as of December 31, 2024
5,351,507
$
10.89
The weighted-average grant date fair value per share of time-based RSUs granted during the years ended December
31, 2024, 2023, and 2022 was $11.53, $10.55, and $11.08, respectively. The total fair value of time-based RSUs that vested
during the years ended December 31, 2024, 2023, and 2022 was $22.0 million, $18.3 million, and $14.8 million, respectively.
Performance-based RSUs
Performance-based RSUs (“PSUs”) are granted to certain executives. PSUs currently outstanding vest upon the
achievement of specified performance criteria over a three-year performance period, generally subject to the executive
remaining in continuous service with the Company through the applicable vesting dates. The performance criteria applicable
to the PSUs granted in 2022 were realizing relative total shareholder return goals (the “Relative TSR PSUs”). The
performance criteria applicable to the PSUs granted in 2024 and 2023 consisted of an equal weighting of (i) Relative TSR
PSUs and (ii) achieving specified stock price targets (the “Absolute TSR PSUs”).
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F-39
The Relative TSR PSUs and Absolute TSR PSUs are valued using the Monte Carlo simulation method on the date of
grant. The weighted average assumptions used to estimate the fair value of Relative TSR PSUs and Absolute TSR PSUs were
as follows for the years ended December 31, 2024, 2023, and 2022:
Year Ended December 31,
2024
2023
2022
Relative
Absolute
Relative
Absolute
Relative
TSR PSUs
TSR PSUs
TSR PSUs
TSR PSUs
TSR PSUs
Fair value of common stock
$
12.41
$
12.41
$
11.39
$
10.74
$
11.13
Expected volatility
38.0 %
38.0 %
37.0 %
37.0 %
41.7 %
Expected term (in years)
3.0
3.0
3.0
3.0
2.8
Risk-free interest rate
4.2 %
4.2 %
4.7 %
4.7 %
1.6 %
Expected dividend yield
— %
— %
— %
— %
— %
A summary of PSU activity for the year ended December 31, 2024 is as follows:
Weighted-
Average
Number
Grant Date
of PSUs
Fair Value
Outstanding as of December 31, 2023
1,653,268
$
14.55
Granted
540,636
14.91
Vested and released
(802,800)
12.84
Forfeited
(282,598)
17.36
Outstanding as of December 31, 2024
1,108,506
$
13.91
The weighted-average grant date fair value per share of PSUs granted during the years ended December 31, 2024,
2023, and 2022 was $14.91, $14.09, and $14.30, respectively. The total fair value of PSUs that vested during the years ended
December 31, 2024, 2023, and 2022 was $9.8 million, $0.8 million and $1.7 million, respectively.
Stock Options
Stock options granted under the Company’s equity plans represent the right to purchase one share of the Company’s
Class A Common Stock pursuant to the terms of the applicable award agreement. Shares of the Company's Class A Common
Stock are delivered to the employee upon exercise, subject to payment of applicable withholding taxes.
The Company ceased granting stock options during the year ended December 31, 2020. Stock options previously
granted under the Company’s equity plans generally have a ten-year term and vest over a period of four years, provided the
individual continues to serve at the Company through the vesting dates. Options granted under all equity plans are exercisable
at a price per share not less than the fair market value of the underlying common stock on the date of grant. The estimated fair
value of options, including the effect of estimated forfeitures, is recognized over the requisite service period, which is
typically the vesting period of each option.
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F-40
The following table summarizes stock option activity under the Company’s share-based compensation plans:
Weighted-
Weighted-
Number of
Average
Average
Aggregate
Stock
Exercise
Contractual
Intrinsic
Options
Price(1)
Life
Value
(in years)
(in thousands)
Outstanding at December 31, 2023
5,836,306
$ 12.36
2.56
$
2,920
Granted
—
—
Exercised
(825,416)
12.19
Cancelled
(470,626)
12.51
Outstanding at December 31, 2024
4,540,264
12.37
1.97
—
Vested or expected to vest at December 31, 2024
4,540,264
12.37
1.97
—
Exercisable at December 31, 2024
4,540,264
12.37
1.97
—
(1)
Amounts relating to stock options granted prior to the separation of the Company’s soluble guanylate cycle business, and certain other assets and
liabilities, into Cyclerion Therapeutics, Inc. (the “Separation) on April 1, 2019 have not been adjusted to reflect the effect of the Separation on the
Company’s stock price.
The total intrinsic value of options exercised during the years ended December 31, 2024, 2023, and 2022 was $2.0
million, $0.2 million, and $0.9 million, respectively. The intrinsic value was calculated as the difference between the fair value
of the Company’s Class A Common Stock at the date of exercise and the exercise price of the option issued.
The following table sets forth the Company's unrecognized share-based compensation expense, net of estimated
forfeitures, as of December 31, 2024, by type of award and the weighted-average period over which that expense is expected
to be recognized:
Unrecognized Weighted-Average
Expense, Net
Remaining
of Estimated
Recognition
Forfeitures
Period
(in thousands)
(in years)
Type of award:
Restricted stock awards
$
513
0.46
Time-based restricted stock units
32,147
2.31
Performance-based restricted stock units
3,015
1.82
The total unrecognized share-based compensation cost will be adjusted for future changes in estimated forfeitures.
14. Income Taxes
The Company is subject to U.S. federal, state, and foreign income taxes. The components of income (loss) before
income taxes during the years ended on December 31, 2024, 2023, and 2022 consisted of the following (in thousands):
Year Ended December 31,
2024
2023
2022
United States
$
167,091
$
226,532
$
252,422
Foreign
(101,893)
(1,174,601)
—
Income (loss) before income taxes
$
65,198
$
(948,069)
$
252,422
The components of the provision for (benefit from) income taxes during the years ended December 31, 2024, 2023,
and 2022 consisted of the following (in thousands):
Year Ended December 31,
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F-41
2024
2023
2022
Current taxes:
Federal
$
—
$
—
$
—
State
(4,487)
10,587
11,618
Foreign
754
346
—
Total current taxes
(3,733)
10,933
11,618
Deferred taxes:
Federal
32,584
47,864
52,191
State
35,467
24,693
13,548
Foreign
—
—
—
Total deferred taxes
68,051
72,557
65,739
Income tax expense
$
64,318
$
83,490
$
77,357
During the year ended December 31, 2024, the Company recorded income tax expense of $64.3 million, comprised
of non-cash tax expense of $57.8 million and cash tax expense of $6.5 million for state income taxes in certain states in which
state taxable income exceeded available net operating losses. During the year ended December 31, 2023, the Company
recorded income tax expense of $83.5 million, comprised of non-cash tax expense of $74.1 million and cash tax expense of
$9.4 million for state income taxes in certain states in which state taxable income exceeded available net operating losses.
During the year ended December 31, 2022, the Company recorded income tax expense of $77.4 million, comprised of non-
cash tax expense of $73.4 million and cash tax expense of $4.0 million for state income taxes in certain states in which state
taxable income exceeded available net operating losses. Due to the Company’s ability to utilize its net operating losses to
offset federal taxable income and taxable income in many states, the majority of the Company’s tax provision is a non-cash
tax expense until the Company’s net operating losses have been fully utilized.
A reconciliation of income taxes computed using the U.S. federal statutory rate of 21% to that reflected in the
consolidated statements of income (loss) are as follows (in thousands):
Year Ended December 31,
2024
2023
2022
Income tax expense (benefit) using U.S. federal statutory rate
$
13,692
$ (199,094)
$
53,009
Acquisition accounting for VectivBio Acquisition
—
139,301
—
Foreign tax rate differential
8,111
93,394
—
Disallowed transaction costs
—
3,424
—
Permanent differences
788
704
(290)
State income taxes, net of federal benefit
10,992
14,024
16,160
Executive compensation - Section 162(m)
2,683
3,979
2,654
Excess tax benefits
749
1,903
3,613
Fair market valuation of Note Hedge Warrants and Convertible Note Hedges
—
(5)
(50)
Tax credits
(1,244)
(79)
(252)
Expiring net operating losses and tax credits
1,187
933
1,087
Effect of change in state tax rate on deferred tax assets and deferred tax liabilities
1,538
2,134
2,581
Change in the valuation allowance
25,564
22,492
(1,155)
Other
258
380
—
Income tax expense
$
64,318
$
83,490
$
77,357
The Company recognizes deferred tax assets and liabilities for the expected future tax consequences of temporary
differences between the financial reporting and tax bases of assets and liabilities. These differences are measured using the
enacted statutory tax rates that are expected to be in effect for the years in which differences are expected to reverse. Deferred
tax assets and liabilities were determined based on the difference between financial statement and tax bases using enacted tax
rates in effect for the year in which the differences are expected to reverse.
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F-42
December 31,
2024
2023
Deferred tax assets:
Net operating loss carryforwards
$
146,978
$
105,401
Tax credit carryforwards
58,494
58,437
Capitalized research and development
22,350
18,267
Share-based compensation
9,508
12,323
Basis difference on collaboration agreement for North America with AbbVie
3,585
80,638
Accruals and reserves
3,804
7,149
Basis difference on Convertible Notes
714
1,613
Intangible assets
3,411
10,968
Operating lease liability
3,892
4,774
Other
1,452
1,810
Total deferred tax assets
254,188
301,380
Deferred tax liabilities:
Fixed assets
(898)
(1,101)
Operating lease right-of-use asset
(2,777)
(2,306)
Total deferred tax liabilities
(3,675)
(3,407)
Net deferred tax asset
250,513
297,973
Valuation allowance
(106,279)
(85,649)
Net deferred tax asset
$
144,234
$
212,324
On a periodic basis, the Company reassesses the valuation allowance on its deferred income tax assets weighing
positive and negative evidence to assess the recoverability of the deferred tax assets. As of December 31, 2024, the Company
maintained a valuation allowance of $106.3 million on deferred tax assets not expected to be realized, related primarily to
deferred tax assets acquired in the VectivBio Acquisition comprised primarily of net operating loss carryforwards in
Switzerland, as well as certain state net operating losses and state tax credits that are expected to expire prior to utilization. As
of December 31, 2023, the Company maintained a valuation allowance of $85.6 million on deferred tax assets not expected to
be realized, related primarily to deferred tax assets acquired in the VectivBio Acquisition comprised primarily of net operating
loss carryforwards in Switzerland, as well as certain tax credits that are expected to expire prior to utilization.
The valuation allowance increased by $20.6 million during the year ended December 31, 2024 primarily to offset the
foreign net operating losses incurred in Switzerland, to offset certain state net operating losses that are expected to expire prior
to utilization, and to offset certain US tax credits that are expected to expire prior to utilization.
The valuation allowance increased by $82.6 million during the year ended December 31, 2023 primarily to offset the
acquired foreign net operating losses from the VectivBio Acquisition, as well as in response to a state tax law change enacted
in October 2023, in which the Company increased its valuation allowance on certain state tax credits that are expected to
expire prior to utilization. Additionally, the Company increased its reserves for uncertain tax positions by $11.0 million in the
second quarter of 2023 in connection with a liability assumed in the VectivBio Acquisition.
Subject to the limitations described below, at December 31, 2024, the Company had federal net operating loss
carryforwards of $260.5 million, of which $130.9 million is subject to expiration between 2035 and 2038 and $129.6 million
may be carried forward indefinitely. As of December 31, 2024, the Company had state net operating loss carryforwards of
$288.0 million to offset future state taxable income, which is subject to expiration at various dates through 2039. The
Company also had tax credit carryforwards of $62.9 million as of December 31, 2024 to offset future federal and state income
taxes, which is subject to expiration at various dates through 2044. The Company had foreign net operating loss carryforwards
of $617.8 million, which are subject to expiration at various dates through 2031.
Utilization of federal and state net operating loss carryforwards and research and development credit carryforwards
may be subject to a substantial annual limitation due to ownership change limitations that could occur in the future in
accordance with Section 382 of the Internal Revenue Code of 1986 (“IRC Section 382”) and with Section 383 of the Internal
Revenue Code of 1986, as well as similar state provisions. These ownership changes may limit the amount of net operating
loss carryforwards and research and development credit carryforwards that can be utilized annually to offset future taxable
income and taxes, respectively. In general, an ownership change, as defined by IRC
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F-43
Section 382, results from transactions increasing the ownership of certain stockholders or public groups in the stock of a
corporation by more than 50 percentage points over a three-year period.
The following table summarizes the changes in the Company’s unrecognized income tax benefits for the years ended
December 31, 2024, 2023, and 2022 (in thousands):
December 31,
2024
2023
2022
Balance at the beginning of the period
$
98,218
$
102,625
$
84,606
Increases based on tax positions related to the current period
4,093
85,446
101,225
Increases for tax positions assumed in VectivBio Acquisition
—
11,372
—
Decreases for tax positions in prior periods
(90,726)
(101,225)
(83,206)
Balance at the end of the period
$
11,585
$
98,218
$ 102,625
The Company had gross unrecognized tax benefits of $11.6 million, $98.2 million, and $102.6 million as
of December 31, 2024, 2023, and 2022, respectively. Of the $11.6 million of total unrecognized tax benefits at December 31,
2024, $7.5 million would, if recognized, affect the Company’s effective tax rate, and the remaining amount would not affect
the Company’s effective tax rate, as it relates to a temporary timing difference. Reserves for uncertain tax positions of $11.8
million and $23.0 million are recorded in other liabilities on the Company’s consolidated balance sheets as of December 31,
2024 and 2023, respectively.
The Company recognizes interest and penalties, if any, related to uncertain tax positions in income tax expense. The
Company recognized $0.8 million, $1.0 million and an insignificant amount of interest and penalties related to uncertain tax
positions during the years ended December 31, 2024, 2023, and 2022, respectively. As of December 31, 2024 and 2023, $5.1
million and $5.2 million of interest and penalties have been accrued, respectively.
The statute of limitations for assessment by the Internal Revenue Service (“IRS”) and state tax authorities is open for
tax years ended December 31, 2021 through the present, although net operating losses generated from years prior to 2021
could be subject to examination and adjustments to the extent utilized in future years. There are currently no federal or state
income tax audits in progress. The statute of limitations for assessment for foreign jurisdictions is open for tax years ended
December 31, 2020 through the present. There are currently no foreign income tax audits in progress.
15. Retirement Plans
Defined Contribution Retirement Plans
The Ironwood Pharmaceuticals, Inc. 401(k) Savings Plan is a defined contribution plan in the form of a qualified
401(k) plan in which substantially all employees are eligible to participate upon employment. Subject to certain IRS limits,
eligible employees may elect to contribute from 1% to 100% of their compensation. Company contributions to the plan are at
the sole discretion of the Company. During the years ended December 31, 2024, 2023, and 2022, the Company provided a
matching contribution equal to the greater of: (a) 100% of employee contributions on the first 3% of eligible compensation
and 50% of employee contributions on the next 3% of eligible compensation; or (b) 75% of the first $10,000 of employee
contributions. During the years ended December 31, 2024, 2023, and 2022, the Company recorded $2.4 million, $2.2 million,
and $2.2 million of expense, respectively, related to its 401(k) company match.
Defined Benefit Retirement Plans
As a result of the VectivBio Acquisition, the Company maintains defined benefit plans for employees in Switzerland
and Belgium, as required by local laws. The pension plans provide employees retirement benefits and risk insurance for death
and disability. The contributions of employers and employees in general are defined in percentages of the insured’s salary. The
retirement pension is calculated based on the old-age credit balance on retirement multiplied by the fixed conversion rate. The
employee has the option to withdraw the capital on demand. The Company updates the estimates used to measure employee
benefit obligations in the fourth quarter and upon a remeasurement event to reflect the updated actuarial assumptions.
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F-44
Defined benefit plans in Switzerland were comprised of a basic plan and management plan during the year ended
December 31, 2023. The participants in the management plan were terminated as of December 31, 2023 and plan assets were
transferred to the participants during the year ended December 31, 2024. The basic plan is the only defined benefit plan in
Switzerland as of December 31, 2024. The defined benefit plan in Belgium was maintained for one employee and has been
terminated as of December 31, 2024.
The following table summarizes the components of net periodic benefit costs (income) for the year ended December
31, 2024 and the period between the acquisition date of June 29, 2023 and December 31, 2023 (in thousands):
December 31,
2024
2023
Current service cost
$
1,032
$
879
Amortization prior service cost
(57)
11
Amortization of unrecognized actuarial gains/(losses)
1,641
124
Interest cost
269
210
Expected return on plan assets
(416)
(235)
Curtailment and other
(2,086)
1,402
Administration costs
9
9
Total
$
392
$
2,400
The amounts recognized in other comprehensive income with respect to the defined benefit pension plans for the year
ended December 31, 2024 and the period between the acquisition date of June 29, 2023 and December 31, 2023 (in
thousands):
December 31,
2024
2023
Amortization prior service cost
$
57
$
(11)
Prior service (cost)/credit arising during financial year
(261)
106
Amortization of unrecognized actuarial gains/(losses)
(1,641)
(124)
Remeasurement (gain)/loss
—
—
Actuarial (gains)/losses arising from plan experience
490
70
Actuarial (gains)/losses arising from demographic assumption
—
989
Actuarial (gains)/losses arising from financial assumptions
906
—
Return on plan assets excluding interest income
(604)
(92)
Expense (income) recognized in other comprehensive income
$
(1,053)
$
938
The amount included in the consolidated statements of financial position arising from the Company’s obligation in
respect to its defined benefit plan as of December 31, 2024, and 2023 (in thousands):
December 31,
2024
2023
Present value of defined benefit obligation
$
(18,462)
$
(37,547)
Fair value of plan assets
15,682
32,992
Net liability arising from defined benefit obligation
$
(2,780)
$
(4,555)
Movements in the present value of the defined benefit obligation for the year ended December 31, 2024, and period
between the acquisition date of June 29, 2023 and December 31, 2023 (in thousands):
December 31,
2024
2023
Beginning defined benefit obligation as of January 1, 2024/June 29, 2023
$
(37,547)
$ (18,865)
Current service cost
(1,032)
(879)
Contributions paid by employees
(837)
(1,214)
Interest expense on defined benefit obligation
(269)
(210)
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F-45
Prior service (cost)/credit arising during financial year
261
(106)
Curtailment
2,086
(1,402)
Remeasurement (gain)/loss on defined benefit obligation
(1,396)
(1,059)
Benefits (paid)/deposited
18,144
(11,813)
Foreign currency exchange (gains)/loss
2,128
(1,999)
Ending defined benefit obligation as of December 31
$
(18,462)
$ (37,547)
Movements in the fair value of plan assets for the year ended December 31, 2024, and period between the acquisition
date of June 29, 2023 and December 31, 2023 (in thousands):
December 31,
2024
2023
Beginning fair value of plan assets as of January 1, 2024/June 29, 2023
$
32,992
$ 16,693
Return on plan assets excluding interest income
416
235
Contributions paid by employer
837
1,215
Contributions paid by employees
837
1,214
Benefits (paid)/deposited
(18,144)
11,813
Actuarial gain/(loss) on plan assets
602
92
Administration expense
(9)
(9)
Foreign currency exchange gains/(losses)
(1,849)
1,739
Ending fair value of plan assets as of December 31
$
15,682
$ 32,992
The allocation of the assets of the different asset classes in the Switzerland basic plan corresponds to (in thousands):
December 31,
2024
2023
Fixed income
$
9,566
61 % $ 12,143
60 %
Equities
3,921
25
5,060
25
Real estate
1,568
10
2,024
10
Other
627
4
1,012
5
Ending fair value of plan assets as of December 31
$ 15,682 100 % $ 20,239 100 %
Assets in the preceding table are predominantly Level 2 assets in the fair value hierarchy, except for certain
mortgage-backed securities valued at $1.9 million and $2.6 million at December 31, 2024 and 2023, respectively, which are
Level 3 assets in the fair value hierarchy.
The amounts reflected in the preceding table as of December 31, 2023 represent the allocation of assets for the
Switzerland basic plan. The allocation of assets for the Switzerland management plan as of December 31, 2023 were not made
available to the Company, as investment decisions are made by plan participants.
Principal assumptions used for the purpose of the actuarial valuations were as follows:
December 31,
2024
2023
Discount rate
1.00 %
1.50 %
Expected return on assets
2.50 %
2.70 %
Expected rate of salary increase
1.65 %
2.25 %
Expected rate of pension increase
— %
— %
Mortality rate
BVG 2020 GT
BVG 2020 GT
Future expected benefit payments based on the assumptions in the preceding table are as follows (in thousands):
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F-46
2025
$
6,502
2026
528
2027
1,055
2028
922
2029 and thereafter
4,276
Total
$
13,283
16. Workforce Reductions and Restructuring
In April 2023, the Company reduced its workforce by approximately 10% of its headquarters-based personnel in an
effort to further strengthen the operational efficiency of the organization. The workforce reduction was substantially
completed during the second quarter of 2023. The Company recorded $3.4 million of restructuring expenses and adjustments,
which are primarily comprised of employee severance, benefits and related costs, during the year ended December 31, 2023.
In June 2023, the Company commenced the elimination of certain positions in connection with the VectivBio
Acquisition. The majority of the eliminations were substantively completed during the year ended December 31, 2023. The
Company recorded $2.6 million and $14.9 million of restructuring expenses, which are primarily comprised of employee
severance, benefits and related costs, during the year ended December 31, 2024 and 2023, respectively.
The following table summarizes the accrued liabilities activity recorded in connection with the reductions in
workforce and related restructuring activities during the year ended December 31, 2024 and 2023, respectively (in thousands):
Amounts
Amounts
Accrued at
Accrued at
December 31, 2023
Charges
Amount Paid Adjustments
December 31, 2024
Headquarters-based workforce reduction
$
270 $
—
(270)
— $
—
VectivBio Acquisition-related workforce reduction
8,102
2,612
(9,990)
(109)
615
Total
$
8,372 $
2,612 $
(10,260) $
(109) $
615
Amounts
Amounts
Accrued at
Accrued at
December 31, 2022
Charges
Amount Paid Adjustments
December 31, 2023
Headquarters-based workforce reduction
$
— $
2,540 $
(2,232) $
(38) $
270
VectivBio Acquisition-related workforce reduction
—
14,903
(7,181)
380
8,102
Total
$
— $ 17,443 $
(9,413) $
342 $
8,372
In January 2025, following an analysis of its strategy and core business needs, and in an effort to streamline focus
and support the continued development of the Company’s pipeline, the Company commenced a reduction in the Company’s
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. The Company estimates that, in connection with this
reduction in its workforce, it will incur aggregate charges of approximately $20.0 million to approximately $25.0 million,
primarily comprised of one-time employee severance and benefit costs. Of these charges, substantially all are expected to
result in cash expenditures. The Company may incur additional costs not currently contemplated due to events associated with
or resulting from the workforce reduction. The estimated charges that the Company expects to incur are subject to a number of
assumptions, and actual results may differ materially from these estimates.
17. Segment Reporting
The Company operates in one reportable business segment—human therapeutics. The human therapeutics segment
revenues are generated primarily through collaborative arrangements and license agreements related to research and
development and commercialization of linaclotide. The accounting policies of the human therapeutics segment are the same as
those described in the summary of significant accounting policies.
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F-47
The Company has identified the Chief Executive Officer and the Chief Financial Officer as the chief operating
decision-maker (“CODM”). The CODM uses consolidated net income (loss) to understand and evaluate the Company’s
operating performance and trends, to prepare and approve the annual budget, and to develop short-term and long-term
operating plans. Revenues, costs and expenses, and other income (expense) are provided to the CODM as presented in the
statement of income (loss). Total assets are not reviewed by the CODM when evaluating the segment’s performance.
18. Selected Quarterly Financial Data (Unaudited)
The following table contains quarterly financial information for the years ended December 31, 2024 and 2023. The
Company believes that the following information reflects all normal recurring adjustments necessary for a fair presentation of
the information for the periods presented. The operating results for any quarter are not necessarily indicative of results for any
future period.
First
Second
Third
Fourth
Total
Quarter
Quarter
Quarter
Quarter
Year
(in thousands, except per share data)
2024
Total revenues
$ 74,877
$
94,396
$ 91,592
$
90,545
$ 351,410
Total cost and expenses
63,857
69,419
65,956
59,054
258,286
Other income (expense), net
(6,062)
(6,101)
(8,267)
(7,496)
(27,926)
Net income (loss)
(4,162)
(860)
3,646
2,256
880
Comprehensive income (loss)
(2,053)
(408)
2,064
5,231
4,834
Net income (loss) per share—basic (1)
(0.03)
(0.01)
0.02
0.01
0.01
Net income (loss) per share—diluted (1)
(0.03)
(0.01)
0.02
0.01
0.01
(1)
The summation of quarterly diluted net income per share does not equate to the calculation for the full fiscal year, as quarterly calculations are
performed on a discrete basis.
First
Second
Third
Fourth
Total
Quarter
Quarter
Quarter
Quarter
Year
(in thousands, except per share data)
2023
Total revenues
$ 104,061
$
107,382
$ 113,739
$ 117,553
$
442,735
Total cost and expenses
43,964
1,190,521
73,716
79,964
1,388,165
Other income (expense), net
5,764
6,917
(8,091)
(7,229)
(2,639)
Net income (loss)
45,714
(1,089,478)
13,950
(1,745)
(1,031,559)
Net income (loss) attributable to Ironwood
Pharmaceuticals, Inc.
45,714
(1,062,187)
15,321
(1,087)
(1,002,239)
Comprehensive income (loss) attributable to
Ironwood Pharmaceuticals, Inc.
45,714
(1,062,187)
14,569
(3,303)
(1,005,207)
Net income per share—basic (1)
0.30
(6.84)
0.10
(0.01)
(6.45)
Net income per share—diluted (1)
0.25
(6.84)
0.09
(0.01)
(6.45)
(1)
The summation of quarterly diluted net income per share does not equate to the calculation for the full fiscal year, as quarterly calculations are
performed on a discrete basis.
Exhibit 19.1
IRONWOOD PHARMACEUTICALS, INC.
INSIDER TRADING PREVENTION POLICY
1.
Policy
The purpose of this policy is to reduce the potential for risk of violating U.S. securities laws by the directors,
officers, other employees, and consultants of Ironwood Pharmaceuticals, Inc. (the “Company”) as well as the
potential for such risk by the members of their families or others who share the same household as the director,
officer, employee, or consultant or other family members whose transactions in Company securities are directed
by the director, officer, employee, or consultant (“Family Members”).
2.
Scope
This policy applies to all Ironwood directors, officers, employees, consultants and their Family Members, as well
as their family trusts, family partnerships and similar entities controlled by them. Directors, officers, employees,
and consultants are responsible for informing their Family Members of, and ensuring their compliance with,
their obligations under this policy. This policy is referenced in the Ironwood Code of Business Conduct and
Ethics.
3.
General Prohibitions
Generally speaking, U.S. securities laws prohibit “insiders” (as defined below) from buying or selling securities
based on material nonpublic information within the meaning of applicable laws. The Company seeks to comply
with such laws and therefore prohibits any employee, officer, director or consultant to the Company from buying
or selling common stock or other securities of the Company (including debentures, bonds and notes), or from
directing trades of any securities of the Company, while that individual is aware of material, nonpublic
information relating to the Company or the applicable security. The Company also prohibits any employee,
officer, director or consultant to the Company from communicating such “material nonpublic information” to
someone else who then acts on it by buying or selling the Company’s securities (known as “tipping”). This
policy also applies to material nonpublic information about any other company with whom the Company is
negotiating or does business (e.g., AbbVie Inc.). You may not trade in the securities of any company on the basis
of such information, nor may you communicate information about any such company to others. Furthermore, the
same restrictions apply to your Family Members and, therefore, you are also responsible for their compliance
with this policy.
On a related point, no one should discuss the Company’s material nonpublic information in public areas—such
as corridors, airplanes and restaurants—and care should be taken in the handling and disposal of company
information, in whatever form or media (papers, computer drives, etc.) containing material nonpublic
information.
The Company has adopted this policy in response to the law and also to avoid even the appearance of improper
conduct by anyone associated with the Company. We have all worked hard to establish the Company’s reputation
for integrity and ethical conduct and cannot afford to have it damaged.
In all cases, the responsibility for determining whether an individual is in possession of material nonpublic
information rests with that individual, and any action on the part of the Company, the Chief Financial Officer or
the Head of Legal (or their designees) or any other employee, officer or director pursuant to this policy (or
otherwise) does not in any way constitute legal advice or insulate an individual from liability under applicable
securities laws. Individuals may be subject to severe legal penalties and disciplinary action by the Company for
any conduct prohibited by this policy or applicable securities laws, as described below in more detail under the
heading “Consequences of Violating this Policy.”
4.
Key Terms
4.1
Insider
Any person who possesses material nonpublic information is considered an insider as to that information.
Insiders include the Company’s directors, officers, employees, independent contractors and those persons in a
special relationship with the Company, e.g., its auditors, consultants or attorneys. The definition of insider
is transaction specific; that is, an individual is an insider with respect to each item of material nonpublic
information of which he or she is aware.
4.2
Material Information
Information is “material” if a reasonable investor would consider it significant in a decision to buy, hold or sell
securities. Put another way, information that could reasonably be expected to affect the price of a security, either
positively or negatively, is material.
Common examples of information that will frequently be regarded as material is information relating to:
◾
prescription results and trends, as well as the associated revenues, for any of the Company’s marketed products;
◾
clinical trial results for any products or product candidates in the Company’s pipeline;
◾
significant new products or discoveries, or significant developments with regard to the Company’s existing
products;
◾
negotiations or other significant developments regarding a licensing arrangement, distribution agreement, joint
venture, collaboration or other contract material to the Company’s business;
◾
pending FDA or other regulatory action;
◾
earnings or loss or other historical financial information;
◾
projections of future earnings or losses or other financial guidance;
◾
a pending or proposed merger, acquisition, tender offer, sale of part of the Company’s business or acquisition of
another business;
◾
impending securities offerings by the Company;
◾
major events regarding the Company’s securities, including a proposed stock split or stock dividend;
◾
changes in management, the Board of Directors or other major changes in personnel;
◾
major litigation developments;
◾
impending financial problems; and
◾
other changes in the status of any of the Company’s activities which may have an adverse or favorable impact.
Other types of information may also be material; no complete list can be given.
4.3
Nonpublic
Information is “nonpublic” or “inside information” until such time that it has been made available to investors
generally and the market has had time to digest it. As a general matter, Ironwood considers two trading days to
be a sufficient period for new information to be absorbed and evaluated by the market.
Whether a particular item is “material” or “nonpublic” will be judged with the benefit of hindsight. Accordingly,
when in doubt as to a particular item of information, you should presume it to be material and not to have been
disclosed to the public. Do not hesitate to contact Ironwood’s Chief Financial Officer or Head of Legal with any
questions on this.
5.
Timing of Transactions
5.1
General Rule
If you know of material nonpublic information about the Company, you should not engage in any securities
transactions before the completion of two full trading days following when the information is publicly
announced in a press release or in a report filed by the Company with the Securities and Exchange Commission.
If the information relates to the Company’s financial performance, you should wait until the completion of the
second trading day after the Company issues its quarterly investor update. There are no
exceptions to the above limitations, even for transactions that may be claimed to be justifiable for independent
reasons (such as the need to raise money for an emergency expenditure).
5.2
Blackout Periods
It is a violation of this policy for directors, “officers” (as defined in Section 16 of the Securities Exchange Act of
1934, as amended (the “Exchange Act”)), and other persons who, because they are in a position to routinely
become aware of material nonpublic information, are designated by the Chief Financial Officer or the Head of
Legal to make any transaction in the market (purchase or sale) during a “blackout period” that covers the period
from two weeks prior to the end of each calendar quarter (i.e., March, June, September and December) until the
completion of two full trading days following the quarterly investor update. In addition, the Chief Financial
Officer, the Head of Legal or their designees may put in place issue-specific additional blackout periods on a
case-by-case basis. If you are named to an issue-specific blackout list, you will be notified by the Chief Financial
Officer, the Head of Legal or their designees and shall remain subject to the prohibition against trading until such
time that the Chief Financial Officer, the Head of Legal or their designees notifies you that the blackout has been
lifted.
5.3
Pre-Clearance
Each director and “officer” (as defined in Section 16 of the Exchange Act) must contact the Chief Financial
Officer, the Head of Legal or their designees at least forty-eight (48) hours prior to making any transaction (e.g.,
purchase, sale or gift) involving the Company’s securities to obtain pre-clearance of such transaction. The
brokers employed by a director or such officer may be required to sign an acknowledgement of the foregoing. If
clearance to engage in a trade is received, you must complete the proposed trade within two trading days or
make a new trading request.
If the Company is in a blackout period, or you are otherwise in possession of material nonpublic information,
you may be asked to postpone your transaction until the blackout period is lifted or you otherwise receive
permission to trade from the Chief Financial Officer, the Head of Legal or their designees.
Any transaction in Company securities by a director or “officer” (as defined in Section 16 of the Exchange Act)
must be reported to the Head of Legal or his or her designee on the same day in which the transaction occurs.
Compliance with this provision is imperative given the requirement of Section 16 of the Exchange Act, that
directors and “officers”(as defined in Section 16 of the Exchange Act) generally must report changes in
ownership of Company securities to the Securities and Exchange Commission within two (2) business days.
Each report should include the date of the transaction, quantity of securities, price and broker-dealer through
which the transaction was effected, in addition to any other information requested by the Company from time to
time.
5.4
Post-Termination Transactions
This policy continues to apply to transactions in Company securities even after an individual has terminated
employment or other services to the Company or a subsidiary, including without limitation, if the individual is
aware of material nonpublic information when the employment or service relationship terminates, he or she may
not engage in any securities transactions before the completion of two full trading days following when the
information is publicly announced in a press release, in a report filed by or furnished to the Company with the
Securities and Exchange Commission or otherwise publicly disseminated. In addition, for the avoidance of
doubt, if the individual is subject to an issue-specific blackout when the employment or service relationship
terminates, he or she will continue to be subject to such blackout until notified by the Chief Financial Officer, the
Head of Legal or their designee.
6.
Stock Options, Restricted Stock Units, Employee Stock Purchase Plan Shares and Transactions
Not Involving a Purchase or Sale
6.1
Stock Options
The restrictions set forth herein do not apply to exercises of stock options in which an employee purchases
shares of Ironwood stock pursuant to such stock options; such option exercises do not require prior approval.
Any sales of shares purchased pursuant to stock options, however, are subject to the restrictions set forth in this
policy. In particular, some “cashless exercises” include both exercises of options and an immediate sale
of stock acquired via the option exercise; therefore, “cashless exercises” which include a sale of securities are
subject to the restrictions set forth herein.
6.2
Restricted Stock Units
Similarly, the restrictions set forth herein do not apply to the issuance of shares from the Company to an
employee upon the vesting of restricted stock units (“RSUs”) and to the sale of such shares by the Company to
satisfy the employee’s tax obligations in connection with the vesting of RSUs, commonly known as “sell-to-
cover,” which are made pursuant to the terms of the restricted stock unit award agreement or under a 10b5-1 Plan
solely authorizing sell-to-cover transactions. However, any other sales of RSUs are subject to the restrictions set
forth in this policy.
6.3
Employee Stock Purchase Plan
Although purchases of Ironwood stock pursuant to the Ironwood Employee Stock Purchase Plan are not subject
to the restrictions set forth herein, all sales of shares purchased pursuant to such plan are subject to all the
restrictions set forth in this policy.
6.4
Transactions Not Involving a Purchase or Sale
Bona fide gifts are not transactions subject to this policy, unless (i) the person making the gift has reason to
believe that the recipient intends to sell the Company securities while the person making the gift is aware of
material nonpublic information or (ii) the person making the gift is subject to the trading restrictions specified
above under the heading “Blackout Periods” and has reason to believe that a sale by the recipient of the
Company securities may occur during a “blackout period.” For the avoidance of doubt, Section 5.3, Pre-
Clearance, of this policy applies to gifts.
7.0
10b5-1 Plans
The above limitations do not apply to transactions done pursuant to a 10b5-1 Plan (as described below). A 10b5-
1 Plan is a contract, instruction or written plan that sets forth a plan to sell securities in the future without any
further investment decision(s) at the time of the actual trade consummation. A 10b5-1 Plan must be established
(or amended, as the case may be) in good faith at a time when you were not aware of material nonpublic
information, and you must act in good faith with respect to the plan. In addition, any modification or change to
the amount, price or timing of a trade under a 10b5-1 Plan constitutes the adoption of a new plan with such
modified terms.
Any document intended to qualify as a 10b5-1 Plan must adhere to the requirements of Rule 10b5-1, including
the restrictions set forth below, and such document (including any amendments thereof) must be reviewed and
approved by the Chief Financial Officer, the Head of Legal or their designees in advance of adoption or
amendment of a 10b-5-1 Plan.
7.1
Cooling-off Period
In addition to the other requirements of Rule 10b5-1, each 10b5-1 Plan, including any plan amendments,
revising the amount, price or timing of a trade under an existing 10b5-1 Plan, must provide for a cooling-off
period prior to the commencement of trading thereunder.
All of Ironwood’s directors and “officers” (as defined in Section 16 of the Exchange Act) are subject to a
cooling-off period between the plan adoption and the commencement of any trading thereunder equal to the later
of (i) ninety (90) days following adoption of the plan; or (ii) two (2) business days after the filing of the
Company’s Form 10-K or Form 10-Q that includes financial results for the quarter during which the plan was
adopted, subject to a maximum cooling-off period of one hundred twenty (120) days.
All others are subject to a cooling-off period of thirty (30) days between plan adoption and the commencement
of any trading thereunder.
8.0
Special and Prohibited Transactions
There is a heightened legal risk and the appearance of improper or inappropriate conduct if directors or
“officers” (as defined in Section 16 of the Exchange Act) engage in certain types of transactions. Therefore,
these individuals may not engage in any of the following transactions:
◾
Short sales. Short sales of Company securities (i.e., the sale of a security that the seller does not own) may
evidence an expectation on the part of the seller that the securities will decline in value, and therefore have the
potential to signal to the market that the seller lacks confidence in the Company’s prospects. In addition, short
sales may reduce a seller’s incentive to seek to improve the Company’s performance. For these reasons, short
sales of Company securities are prohibited.
◾
Publicly-traded options. Given the relatively short term nature of publicly-traded options, transactions in
options may create the appearance that a director or officer is trading based on material nonpublic information
and focus such person’s attention on short-term performance at the expense of the Company’s long-term
objectives. Accordingly, transactions in put options, call options or other derivative securities, on an exchange
or in any other organized market, are prohibited by this policy.
◾
Hedging transactions. Hedging or monetization transactions can be accomplished through a number of
possible mechanisms, including through the use of financial instruments such as prepaid variable forwards,
equity swaps, collars and exchange funds. Such hedging transactions may permit a director or officer to
continue to own Company securities obtained through employee equity incentive plans or otherwise, but
without the full risks and rewards of ownership. When that occurs, the director or officer may no longer have
the same objectives as the Company’s other stockholders, and therefore they are prohibited from engaging in
any such transactions.
◾
Margin Accounts and Pledges. Securities held in a margin account or pledged as collateral for a loan may be
sold without consent by the broker if an individual fails to meet a margin call or by the lender in foreclosure if
an individual defaults on the loan. Because a margin or foreclosure sale that occurs when an individual is
aware of material nonpublic information or otherwise is not permitted to trade in Company securities would
violate this Policy, directors and “officers” (as defined in Section 16 of the Exchange Act) are prohibited from
holding Company securities in a margin account or pledging Company securities as collateral for a loan. An
exception may be granted where an individual wishes to pledge Company securities as collateral for a loan and
clearly demonstrates the financial capacity to repay the loan without resorting to the pledged securities. If any
such individual wishes to pledge Company securities as collateral for a loan, he or she must submit a request
to the Head of Legal or his or her designee prior to the proposed execution of documents evidencing the
proposed pledge.
9.0
Consequences of Violating this Policy
9.1
The Law
U.S. laws impose heavy penalties on those who, in violation of law, either buy or sell securities while aware of
material nonpublic information or pass the material nonpublic information along to others who use it to buy or
sell securities. Potential punishments include a range of civil and criminal penalties, as well as the potential for
imprisonment.
9.2
Company Sanctions
In view of the seriousness of this matter, the Company may discipline any person who violates this policy by any
appropriate means, including dismissal for cause. Any of these consequences, and even an investigation that does
not result in prosecution, can tarnish your reputation and irreparably damage you and the Company.
10.0
Company Assistance & Waivers
Anyone with questions about specific transactions may obtain additional guidance from the Chief Financial
Officer or the Head of Le gal. Please contact the Chief Financial Officer or the Head of Legal if you believe
that a waiver under a provision of this policy is warranted. The Chief Financial Officer or the Head of Legal
must obtain the approval of the CEO to grant a waiver hereunder in certain limited circumstances. In addition, a
majority of the independent directors or the Audit Committee of the Board of Directors must approve a waiver
for the CEO or any director.
Exhibit 21.1
List of Registrant’s Subsidiaries
Ironwood Pharmaceuticals Securities Corporation (Massachusetts)
Ironwood Pharmaceuticals GmbH (Switzerland)
VectivBio AG (Switzerland)
GlyPharma Therapeutic Inc (Canada)
CONSENT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM
We consent to the incorporation by reference in the following Registration Statements:
(1) Registration Statement (Form S-8 No. 333-275436) pertaining to Amended and Restated 2019 Equity
Incentive Plan of Ironwood Pharmaceuticals, Inc.;
(2) Registration Statements (Form S-3 Nos. 333-275435, 333-179430, 333-199885, 333-221294, and 333-
249896) of Ironwood Pharmaceuticals, Inc.;
(3) Registration Statement (Form S-8 No. 333-231887) pertaining to the 2019 Equity Incentive Plan of
Ironwood Pharmaceuticals, Inc.;
(4) Registration Statements (Form S-8 Nos. 333-189340, 333-197875, 333-206228, 333-213001, 333-
219670, 333-226613, and 333-231890) pertaining to the Amended and Restated 2010 Employee Stock
Purchase Plan of Ironwood Pharmaceuticals, Inc.;
(5) Registration Statements (Form S-8 Nos. 333-184396, 333-189339, 333-197874, 333-206227, 333-
213002, 333-219669, and 333-226612) pertaining to the Amended and Restated 2010 Employee,
Director and Consultant Equity Incentive Plan of Ironwood Pharmaceuticals, Inc.;
(6) Registration Statement (Form S-8 No. 333-165230) pertaining to the 2010 Employee Stock Purchase
Plan of Ironwood Pharmaceuticals, Inc.;
(7) Registration Statement (Form S-8 No. 333-165231) pertaining to the 2010 Employee, Director and
Consultant Equity Incentive Plan of Ironwood Pharmaceuticals, Inc.;
(8) Registration Statement (Form S-8 No. 333-165228) pertaining to the Amended and Restated 2005
Stock Incentive Plan of Ironwood Pharmaceuticals, Inc.;
(9) Registration Statement (Form S-8 No. 333-165229) pertaining to the Amended and Restated 2002
Stock Incentive Plan of Ironwood Pharmaceuticals, Inc.; and
(10) Registration Statement (Form S-8 No. 333-165227) pertaining to the 1998 Amended and Restated
Stock Option Plan of Ironwood Pharmaceuticals, Inc.;
of our reports dated March 31, 2025, with respect to the consolidated financial statements of Ironwood
Pharmaceuticals, Inc. and the effectiveness of internal control over financial reporting of Ironwood
Pharmaceuticals, Inc. included in this Annual Report (Form 10-K) of Ironwood Pharmaceuticals, Inc. for the
year ended December 31, 2024.
/s/ Ernst & Young LLP
Boston, Massachusetts
March 31, 2025
EXHIBIT 23.1
EXHIBIT 31.1
CERTIFICATION PURSUANT
TO RULE 13a-14(a) UNDER
THE SECURITIES EXCHANGE ACT OF 1934
I, Thomas McCourt, certify that:
1.
I have reviewed this Annual Report on Form 10-K of Ironwood Pharmaceuticals, Inc. (the “registrant”);
2.
Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a
material fact necessary to make the statements made, in light of the circumstances under which such statements were
made, not misleading with respect to the period covered by this report;
3.
Based on my knowledge, the financial statements, and other financial information included in this report, fairly
present in all material respects the financial condition, results of operations and cash flows of the registrant as of, and
for, the periods presented in this report;
4.
The registrant’s other certifying officer and I are responsible for establishing and maintaining disclosure controls and
procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting
(as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:
a.
Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be
designed under our supervision, to ensure that material information relating to the registrant, including its
consolidated subsidiaries, is made known to us by others within those entities, particularly during the period
in which this report is being prepared;
b.
Designed such internal control over financial reporting, or caused such internal control over financial
reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of
financial reporting and the preparation of financial statements for external purposes in accordance with
generally accepted accounting principles;
c.
Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report
our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period
covered by this report based on such evaluation; and
d.
Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred
during the registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual
report) that has materially affected, or is reasonably likely to materially affect, the registrant’s internal
control over financial reporting; and
5.
The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control
over financial reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or
persons performing the equivalent functions):
a.
All significant deficiencies and material weaknesses in the design or operation of internal control over
financial reporting which are reasonably likely to adversely affect the registrant’s ability to record, process,
summarize and report financial information; and
b.
Any fraud, whether or not material, that involves management or other employees who have a significant
role in the registrant’s internal control over financial reporting.
Date: March 31, 2025
/s/ Thomas McCourt
Thomas McCourt
Chief Executive Officer
EXHIBIT 31.2
CERTIFICATION PURSUANT
TO RULE 13a-14(a) UNDER
THE SECURITIES EXCHANGE ACT OF 1934
I, Greg Martini, certify that:
1.
I have reviewed this Annual Report on Form 10-K of Ironwood Pharmaceuticals, Inc. (the “registrant”);
2.
Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a
material fact necessary to make the statements made, in light of the circumstances under which such statements were
made, not misleading with respect to the period covered by this report;
3.
Based on my knowledge, the financial statements, and other financial information included in this report, fairly
present in all material respects the financial condition, results of operations and cash flows of the registrant as of, and
for, the periods presented in this report;
4.
The registrant’s other certifying officer and I are responsible for establishing and maintaining disclosure controls and
procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting
(as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:
a.
Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be
designed under our supervision, to ensure that material information relating to the registrant, including its
consolidated subsidiaries, is made known to us by others within those entities, particularly during the period
in which this report is being prepared;
b.
Designed such internal control over financial reporting, or caused such internal control over financial
reporting to be designed under our supervision, to provide reasonable assurance regarding the reliability of
financial reporting and the preparation of financial statements for external purposes in accordance with
generally accepted accounting principles;
c.
Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report
our conclusions about the effectiveness of the disclosure controls and procedures, as of the end of the period
covered by this report based on such evaluation; and
d.
Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred
during the registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual
report) that has materially affected, or is reasonably likely to materially affect, the registrant’s internal
control over financial reporting; and
5.
The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control
over financial reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or
persons performing the equivalent functions):
a.
All significant deficiencies and material weaknesses in the design or operation of internal control over
financial reporting which are reasonably likely to adversely affect the registrant’s ability to record, process,
summarize and report financial information; and
b.
Any fraud, whether or not material, that involves management or other employees who have a significant
role in the registrant’s internal control over financial reporting.
Date: March 31, 2025
/s/ Gregory Martini
Gregory Martini
Chief Financial Officer
EXHIBIT 32.1
CERTIFICATION PURSUANT TO
18 U.S.C. SECTION 1350,
AS ADOPTED PURSUANT TO
SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002
In connection with the Annual Report of Ironwood Pharmaceuticals, Inc. (the “Company”) on Form 10-K for the
period ended December 31, 2024 as filed with the Securities and Exchange Commission on the date hereof (the “Report”), I,
Thomas McCourt, Chief Executive Officer of the Company, certify, pursuant to 18 U.S.C. Section 1350, as adopted pursuant
to Section 906 of the Sarbanes-Oxley Act of 2002, to my knowledge that:
(1)
The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of
1934, as amended; and
(2)
The information contained in the Report fairly presents, in all material respects, the financial condition and
results of operations of the Company.
/s/ Thomas McCourt
Thomas McCourt
Chief Executive Officer
March 31, 2025
A signed original of this written statement required by Section 906 has been provided to the Company and will be
retained by the Company and furnished to the Securities and Exchange Commission or its staff upon request.
EXHIBIT 32.2
CERTIFICATION PURSUANT TO
18 U.S.C. SECTION 1350,
AS ADOPTED PURSUANT TO
SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002
In connection with the Annual Report of Ironwood Pharmaceuticals, Inc. (the “Company”) on Form 10-K for the
period ended December 31, 2024 as filed with the Securities and Exchange Commission on the date hereof (the “Report”), I,
Greg Martini, Chief Financial Officer of the Company, certify, pursuant to 18 U.S.C. Section 1350, as adopted pursuant to
Section 906 of the Sarbanes-Oxley Act of 2002, to my knowledge that:
(1)
The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of
1934, as amended; and
(2)
The information contained in the Report fairly presents, in all material respects, the financial condition and
results of operations of the Company.
/s/ GREGORY MARTINI
Gregory Martini
Chief Financial Officer
March 31, 2025
A signed original of this written statement required by Section 906 has been provided to the Company and will be
retained by the Company and furnished to the Securities and Exchange Commission or its staff upon request.