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The trading price of our Class A Common Stock may decline due to these risks.
−Removed: Risks Related to Our Business and Industry
+Added: Risks Related to Commercializing LINZESS and Other Product Candidates
We are highly dependent on the commercial success of LINZESS (linaclotide) in the United States, or the U.S., for the foreseeable future;
we cannot guarantee that we will generate sufficient revenues from LINZESS to cover our expenses.
−Removed: We and our partner, Allergan plc (together with its affiliates), or Allergan, began selling LINZESS in the U.S.
−Removed: during December 2012.
+Added: We and our partner, AbbVie Inc.
+Added: (together with its affiliates), or AbbVie, (successor to Allergan plc (together with its affiliates), or Allergan), began selling LINZESS in the U.S.
+Added: 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.
2 unchanged sentences
● the size of the treatable patient population;
−Removed: ● the effectiveness of the sales, managed markets and marketing efforts by us and Allergan;
+Added: ● the effectiveness of the sales, managed markets and marketing efforts by us and AbbVie, including our ability to adapt our commercial model and market strategy to the evolving landscape;
● the adoption of LINZESS by physicians, which depends on whether physicians view it as safe and effective treatment for adult patients with IBS-C and CIC;
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In addition, the U.S.
−Removed: Food and Drug Administration, or U.S.
FDA-approved label for LINZESS contains a boxed warning about its use in pediatric patients.
1 unchanged sentence
There is also a warning advising physicians to avoid the use of LINZESS in pediatric patients six to less than 18 years of age.
−Removed: This warning is based on data in young juvenile mice and the lack of clinical safety and efficacy data in pediatric patients of any age group.
−Removed: We and Allergan have established a nonclinical and clinical post-marketing plan with the U.S.
−Removed: FDA to understand the safety and efficacy of LINZESS in pediatric patients, which is discussed below.
+Added: This warning is based on data in young juvenile mice and, at the time of approval, the lack of pediatric clinical safety and efficacy data.
+Added: We and AbbVie have established a nonclinical and clinical post-marketing plan with the U.S.
+Added: FDA to understand the safety and efficacy of LINZESS in pediatric patients.
These and other restrictions could limit the commercial potential of LINZESS.
−Removed: We rely entirely on contract manufacturers, our partners and other third parties to manufacture linaclotide and our other product candidates and distribute linaclotide.
−Removed: 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.
−Removed: We have no internal manufacturing or distribution capabilities.
−Removed: Instead, we rely on a combination of contract manufacturers and our partners to manufacture active pharmaceutical ingredient, or API, finished drug product and finished goods for linaclotide and our other product candidates.
−Removed: Beginning in 2020, each of our partners for linaclotide will be 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.
−Removed: 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.
−Removed: We or our partners have commercial supply agreements with independent third parties to manufacture linaclotide API.
−Removed: Each of our partners and the third-party manufacturers we or our partners engage must comply with current good manufacturing practices, or GMP, and other stringent regulatory requirements enforced by the U.S.
−Removed: FDA and foreign regulatory authorities in other jurisdictions.
−Removed: 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.
−Removed: Manufacturers of our products may be unable to comply with these GMP requirements and with other regulatory requirements.
−Removed: We have little control over compliance with these regulations and standards by our partners and the third-party manufacturers we or our partners engage.
−Removed: 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 and natural disasters.
−Removed: In addition, the raw materials necessary to make API for our products are acquired from a limited number of sources.
−Removed: Any delay or disruption in the availability of these raw materials or a change in raw material suppliers could result in production disruptions, delays or higher costs with consequent adverse effects on us.
−Removed: The manufacture of pharmaceutical products requires significant expertise and capital investment, including the development of advanced manufacturing techniques and process controls.
−Removed: Manufacturers of pharmaceutical products often encounter difficulties in commercial production.
−Removed: 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.
−Removed: 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.
−Removed: Finding alternative manufacturers or adding additional manufacturers requires a significant amount of time and involves significant expense.
−Removed: 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.
−Removed: 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 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.
−Removed: 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.
−Removed: 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.
−Removed: or in the other countries where it is approved, or the ability to achieve regulatory approval, launch and commercialize linaclotide in other territories.
−Removed: We work jointly and collaboratively with partners on many aspects of the development, manufacturing and/or commercialization of linaclotide.
−Removed: 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.
−Removed: Further, the success of our collaborations is highly dependent on the resources, efforts and skills of our partners and their key employees.
−Removed: As we and our partners develop and commercialize linaclotide in the U.S.
−Removed: 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.
−Removed: In June 2019, Allergan and AbbVie, Inc., or AbbVie, entered into a definitive agreement providing for the combination of the two companies.
−Removed: If the transaction is completed, or if any of our linaclotide partners otherwise undergo a change of control or in management, we would need to reestablish many relationships and confirm continued alignment on our development and commercialization strategy for linaclotide.
−Removed: 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.
−Removed: 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.
−Removed: 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.
−Removed: 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 reacquire that partner’s rights with respect to linaclotide.
−Removed: 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.
−Removed: We have assembled a team that represents the functional areas necessary to support the commercialization of LINZESS in the U.S.
−Removed: If Allergan was subject to a change of control that allowed us to further commercialize LINZESS in the U.S.
−Removed: 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 Allergan was previously providing to the collaboration.
−Removed: 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.
−Removed: Although many members of our global operations, commercial and medical affairs teams have strategic oversight of, and a certain level of involvement in, their functional areas globally, we do not have corresponding operational capabilities in these areas outside of the U.S.
−Removed: If Allergan, Astellas Pharma, Inc., or Astellas, or AstraZeneca AB (together with its affiliates), 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.
−Removed: 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.
−Removed: In any of these situations, the development and commercialization of linaclotide could be negatively impacted.
−Removed: We must work effectively and collaboratively with Allergan to market and sell LINZESS in the U.S.
−Removed: for it to achieve its maximum commercial potential.
−Removed: We are working closely with Allergan to execute our joint commercialization plan for LINZESS.
−Removed: The commercialization plan includes an agreed upon marketing campaign that targets the physicians who see patients who could benefit from LINZESS treatment.
−Removed: Our marketing campaign also targets the adult men and women who suffer from IBS-C or CIC.
−Removed: Our commercialization plan also includes an integrated call plan for our sales forces to optimize the education of specific gastroenterologists and primary care physicians on whom our and Allergan’s sales representatives call, and the frequency with which the representatives meet with them.
−Removed: In order to optimize the commercial potential of LINZESS, we and Allergan must execute upon this commercialization plan effectively and efficiently.
−Removed: In addition, we and Allergan must continually assess and modify our commercialization plan in a coordinated and integrated fashion in order to adapt to the promotional response.
−Removed: Further, we and Allergan must continue to focus and refine our marketing campaign to ensure a clear and understandable physician-patient dialogue around IBS-C, CIC and the potential for LINZESS as an appropriate therapy.
−Removed: In addition, we and Allergan must provide our sales forces with the highest quality support, guidance and oversight for them to continue to effectively promote LINZESS to gastroenterologists and primary care physicians.
−Removed: Should the merger of Allergan and AbbVie be consummated, we and AbbVie must work together to ensure an orderly transition of this work plan and to continue these commercialization efforts.
−Removed: If we and Allergan (or AbbVie, should the merger be consummated) fail to 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.
−Removed: Our 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 are subject to uncertainty relating to pricing and reimbursement policies in the U.S.
which, if not favorable for our products, could hinder or prevent our products’ commercial success.
−Removed: Our and our partner’s ability to commercialize our products successfully depend in part on the coverage and reimbursement levels set by governmental authorities, private health insurers and other third-party payors.
+Added: 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 over-the-counter alternatives.
−Removed: Further, in order to obtain and maintain acceptable reimbursement levels and access for patients at copay levels that are reasonable and customary, we may face increasing pressure to offer discounts or rebates from list prices or discounts to a greater number of third-party payors or other unfavorable pricing modifications.
−Removed: Obtaining and maintaining favorable reimbursement can be a time consuming and expensive process, and there is no guarantee that we or Allergan 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.
+Added: 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.
+Added: Obtaining and maintaining favorable reimbursement can be a time consuming and expensive process, and there is no guarantee that we or AbbVie 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 even refuse to provide, reimbursement for our products, and others may do so in the future.
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or if reimbursement is not maintained at satisfactory levels or becomes subject to prior authorization.
−Removed: 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.
+Added: In addition, our business could be adversely
+Added: 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.
+Added: Moreover, as discussed further below, 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, as well as the impacts to healthcare access or administration (including, for example, limitations on medications or procedures deemed “non-essential,” reduced interaction between patients and physicians, and increased unemployment), due to the COVID-19 pandemic may materially harm our business and commercialization efforts.
We expect to experience pricing pressures in connection with the sale of our current and future products due to the healthcare reforms discussed below, 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.
−Removed: There have been a number of recent 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.
+Added: 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.
For example, the Bipartisan Budget Act of 2018 contained various provisions that affect coverage and reimbursement of drugs, including an increase, which began in 2019, in the discount that manufacturers of Medicare Part D brand name drugs must provide to Medicare Part D beneficiaries during the coverage gap from 50% to 70%.
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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.
−Removed: 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 Allergan is currently commercializing CONSTELLA in a number of European countries, including the United Kingdom, Italy and Spain.
+Added: 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, including the United Kingdom, Italy and Spain.
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.
−Removed: In the first quarter of 2019, the Chinese National Medical Products Administration approved the marketing application for LINZESS for adults with IBS-C in China, and our partner, AstraZeneca, launched LINZESS in November 2019.
+Added: In addition, LINZESS was first launched in China for the treatment of IBS-C in adults in November 2019, and
+Added: 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 LINZESS in Japan and China.
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or LINZESS in Japan or China, or if coverage and reimbursement for either CONSTELLA or LINZESS is limited or reduced.
−Removed: If our partners are not able to obtain 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.
+Added: 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.
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Any of the foregoing or other consequences could adversely impact our reputation, financial results and business.
−Removed: Because we work with partners to develop, manufacture and commercialize linaclotide, we 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.
−Removed: Allergan played a significant role in the conduct of the clinical trials for linaclotide and in the subsequent collection and analysis of data, and Allergan holds the new drug application, or NDA, for LINZESS.
−Removed: In addition, we are
−Removed: commercializing LINZESS in the U.S.
−Removed: with Allergan.
−Removed: Allergan 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).
−Removed: Allergan is commercializing LINZESS in Mexico and CONSTELLA in Canada, as well as commercializing CONSTELLA in certain countries in Europe.
−Removed: Astellas and AstraZeneca are responsible for development and commercialization of LINZESS in Japan and China (including Hong Kong and Macau), respectively.
−Removed: Beginning in 2020, each of our partners for linaclotide will be 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.
−Removed: We or our partners have commercial supply agreements with independent third parties to manufacture the linaclotide API.
−Removed: 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.
−Removed: 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.
−Removed: Our linaclotide partnering strategy imposes obligations, risks and operational requirements on us as the central node in our global network of partners.
−Removed: 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.
−Removed: Further, we have limited ability to control the amount or timing of resources that our partners devote to linaclotide.
−Removed: If any of our partners fails to devote sufficient time and resources to linaclotide, or if its performance is substandard, 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.
−Removed: 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.
−Removed: 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.
−Removed: If any of our partners competes with us or assists our competitors, it could harm our competitive position.
−Removed: In addition, adverse event reporting requires significant coordination with our partners and third parties.
−Removed: 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, and each of Astellas, AstraZeneca and Allergan is responsible for reporting adverse event information from its territory to us.
−Removed: An AstraZeneca partner is the holder of the global safety database for lesinurad and is responsible for coordinating the safety surveillance and adverse event reporting efforts worldwide with respect to lesinurad.
−Removed: If we or AstraZeneca’s partner fails to perform such activities and maintain each safety database or if such parties do not report adverse events related to such products, 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.
−Removed: FDA or a foreign regulatory authority regarding such products.
−Removed: Furthermore, we or such parties may fail to adequately monitor, identify or investigate adverse events, or to report adverse events to the U.S.
−Removed: FDA or foreign regulatory authority accurately and within the prescribed timeframe.
−Removed: If we or such parties 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 such products, removal of such products from the market, criminal prosecution, the imposition of civil monetary penalties, seizure of such products, or delay in approval of future products.
+Added: We must work effectively and collaboratively with AbbVie 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.
+Added: We are working closely with AbbVie to execute our joint commercialization plan for LINZESS.
+Added: The commercialization plan includes an agreed upon marketing campaign that targets the physicians who see patients who could benefit from LINZESS treatment.
+Added: Our marketing campaign also targets the adult men and women who suffer from IBS-C or CIC.
+Added: Our commercialization plan also includes an integrated call plan for our sales forces in an effort to optimize the education of specific gastroenterologists and primary care physicians on whom our and AbbVie’s sales representatives call, and the frequency with which the representatives meet with them.
+Added: In addition, we are advancing a hybrid (virtual and in-person) selling model and access to technologies such as telehealth in an effort to expand the commercial potential of LINZESS and our other product candidates in the U.S.
+Added: In order to optimize the commercial potential of LINZESS, we and AbbVie must execute upon this commercialization plan effectively and efficiently.
+Added: 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.
+Added: For example, the increase in virtual customer support and limitations on customer access by our customer-facing employees that was prompted by the COVID-19 pandemic contributed to our decision to make virtual promotion a more permanent component of our overall selling model and may further change our commercial model or the market strategy in the industry.
+Added: Further, we and AbbVie must continue to focus and refine our marketing campaign to ensure a clear and understandable physician-patient dialogue around IBS-C, CIC and the potential for LINZESS as an appropriate therapy.
+Added: In addition, we and AbbVie must provide our sales forces with the highest quality support, guidance and oversight for them to continue to effectively promote LINZESS to gastroenterologists and primary care physicians.
+Added: 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.
+Added: Our 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.
+Added: In addition, most of our customer-facing employees are engaged in in-person work practices;
+Added: however, they are limited in the number of in-person details they are able to conduct due to containment and mitigation measures related to the COVID-19 pandemic.
+Added: We monitor the impact of the COVID-19 pandemic in the territories where our customer-facing employees are engaged in in-person work practices, and in some cases, we have paused the in-person work practices as a result of the impact of the COVID-19 pandemic in those territories, and may do so again in the future.
+Added: Customer-facing employees who are not providing in-person services continue to support their customers virtually through telephone and web-based technologies.
+Added: Headquarters employees are expected to have the option to work remotely through mid-2021.
+Added: We may delay, stop or otherwise limit in-person work in the future pending relevant health authority guidance and other safety considerations.
+Added: T he virtual support we continue to provide to customers may not be
+Added: as effective as in-person efforts, and our in-person efforts may be limited and/or limited in their effectiveness.
+Added: If this were to occur, or if we, AbbVie or any of our partners were unable to align on our strategy and development and commercial efforts as a result of the COVID-19 pandemic or otherwise, we may not be able to maintain or increase the revenues that we generate or our business may be otherwise materially harmed.
+Added: 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.
+Added: The pharmaceutical industry and the markets in which we operate are intensely competitive.
+Added: We compete in the marketing and sale of our products, the development of new products and the acquisition of rights to new products with commercial potential.
+Added: Certain of our competitors have substantially greater financial, technical and human resources than us.
+Added: 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.
+Added: 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.
+Added: 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.
+Added: These developments may render our products obsolete or noncompetitive.
+Added: Linaclotide competes with certain prescription therapies and over-the-counter products, including with products that have attained significant levels of market acceptance.
+Added: The availability of prescription competitors and over-the- counter products could limit the demand, and the price we are able to charge, for LINZESS unless we are able to achieve and maintain market acceptance among the medical community and patients and differentiate LINZESS on the basis of its cost and/or actual or perceived benefits.
+Added: For example, Takeda’s AMITIZA (lubiprostone) is approved by the U.S.
+Added: FDA for sale in the U.S.
+Added: for the treatment of IBS-C, CIC and opioid-induced constipation, and an authorized generic version of AMITIZA became available in the U.S.
+Added: in January 2021 and is being commercialized by Endo International plc;
+Added: Bausch Health’s TRULANCE (plecanatide) is approved by the U.S.
+Added: FDA for sale in the U.S.
+Added: for the treatment of adults with IBS-C and CIC;
+Added: Takeda’s MOTEGRITY (prucalopride) is approved by the U.S.
+Added: FDA for sale in the U.S.
+Added: for the treatment of CIC in adults;
+Added: and Alfasigma USA’s ZELNORM (tegaserod) is approved for sale in the U.S.
+Added: for treatment of IBS-C in women under the age of 65.
+Added: Over-the-counter laxatives such as MiraLAX® and DULCOLAX®, and lactulose, a prescription laxative treatment, are also available for the treatment of constipation.
+Added: Additionally, we believe other companies are developing products which could compete with linaclotide, should they be approved by the U.S.
+Added: FDA or foreign regulatory authorities and become commercially available.
+Added: For example, although not currently commercially available, the U.S.
+Added: FDA approved Ardelyx, Inc.’s IBSRELA™ (tenapanor) for the treatment of IBS-C in adults.
+Added: 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.
+Added: If our current or potential competitors are successful in completing drug development for their drug candidates and obtain approval from the U.S.
+Added: FDA or foreign regulatory authorities, they could limit the demand for linaclotide.
Even though LINZESS is approved by the U.S.
2 unchanged sentences
FDA approved LINZESS as a once-daily treatment for adult men and women suffering from IBS-C or CIC.
−Removed: Although we and Allergan completed additional nonclinical and clinical studies in adults that were required by the U.S.
−Removed: FDA in connection with the approval of LINZESS, LINZESS remains subject to ongoing U.S.
+Added: Although we and AbbVie completed additional nonclinical and clinical studies in adults that were required by the U.S.
+Added: FDA in connection with the approval of LINZESS, LINZESS remains subject to ongoing
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.
1 unchanged sentence
There is also a boxed warning advising physicians to avoid the use of LINZESS in pediatric patients six to less than 18 years of age.
−Removed: This warning is based on data in young juvenile mice and the lack of clinical safety and efficacy data in pediatric patients of
−Removed: any age group.
−Removed: We and Allergan have established a nonclinical and clinical post-marketing plan with the U.S.
−Removed: FDA to understand the safety and efficacy of LINZESS in pediatric patients, and clinical pediatric programs in IBS-C and functional constipation currently are ongoing.
+Added: This warning is based on data in young juvenile mice and, at the time of approval, the lack of pediatric clinical safety and efficacy data.
+Added: We and AbbVie have established a nonclinical and clinical post-marketing plan with the U.S.
+Added: FDA to understand the safety and efficacy of LINZESS in pediatric patients, and clinical pediatric programs in IBS-C and functional constipation are ongoing.
Our ability to expand the indication or label information for LINZESS to pediatrics will depend on, among other things, our successful completion of pediatric clinical programs.
−Removed: In addition, as the holder of the approved NDA for each of ZURAMPIC and DUZALLO, we are obligated to monitor and report adverse events and any failure of such products to meet the specifications in the applicable NDA, to submit new or supplemental applications and to obtain U.S.
−Removed: FDA approval for certain changes to such products, including changes to product labeling and manufacturing processes.
+Added: In addition, as the holder of the approved NDA for ZURAMPIC, we are obligated to monitor and report adverse events and any failure of
+Added: ZURAMPIC to meet the specifications in the NDA, to submit new or supplemental applications and to obtain U.S.
+Added: FDA approval for certain changes, including changes to product labeling and manufacturing processes.
These post-approval requirements impose burdens and costs on us.
25 unchanged sentences
If any of the foregoing were to occur, our receipt of regulatory approval in the applicable jurisdiction could be delayed or we may never receive approval at all.
−Removed: 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.
+Added: Additionally, we cannot be certain of the duration or extent to which the COVID-19 pandemic may impact operations of regulatory authorities in jurisdictions around the world, and any reduction in resources dedicated to review and approval of products in applicable jurisdictions could delay or otherwise impact approval or other regulatory decisions or actions.
+Added: 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
+Added: negative effect on the regulatory processes in others.
If linaclotide is not approved for all indications or patient populations or with the label requested, this would limit the uses of linaclotide and have an adverse effect on its commercial potential or require costly post-marketing studies.
+Added: Risks Related to Our Growth Strategy
+Added: 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.
+Added: 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 gastrointestinal products or product candidates or engaging in other transactions with value creation potential.
+Added: The success of this strategy depends upon our ability to identify, select and acquire promising assets, platforms or other opportunities.
+Added: The process of proposing, negotiating and implementing a license or acquisition is lengthy and complex.
+Added: 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.
+Added: 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.
+Added: 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.
+Added: 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 our business and prospects would be materially and adversely affected.
+Added: In addition, such in-licenses, acquisitions or other transactions may entail numerous operational and financial risks, including:
+Added: ● development, regulatory and commercialization challenges;
+Added: ● exposure to unknown liabilities;
+Added: ● disruption of our business and diversion of our management’s time and attention to develop acquired products, product candidates, businesses or technologies;
+Added: ● incurrence of substantial debt, dilutive issuances of securities or depletion of cash to pay for acquisitions;
+Added: ● higher than expected acquisition and integration costs;
+Added: ● difficulty in combining the operations and personnel of any acquired businesses with our operations and personnel;
+Added: ● increased amortization expenses;
+Added: ● impairment of relationships with key suppliers or customers of any acquired businesses due to changes in management and ownership;
+Added: ● inability to motivate key employees of any acquired businesses.
+Added: The development of product candidates in particular is a highly uncertain process, as we discuss further below.
+Added: Any product candidate that we in-license or acquire may require additional development efforts prior to commercial sale, including extensive clinical testing and approval by the U.S.
+Added: FDA and applicable foreign regulatory authorities.
+Added: 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.
+Added: 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.
+Added: 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.
+Added: 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.
+Added: 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.
+Added: As part of our growth strategy, we intend to explore further linaclotide development opportunities.
+Added: 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.
+Added: These development efforts may fail or may not increase the revenues that we generate from LINZESS.
+Added: 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 U.S.
+Added: FDA or in other
+Added: countries or harm linaclotide’s reputation in the marketplace, each of which could materially harm our revenues from linaclotide.
+Added: The strength of our company’s pipeline will depend in large part on the outcomes of studies of assets in our pipeline.
+Added: We may spend several years and make significant investments in developing any current or future product candidate, and failure may occur at any point.
+Added: Our product candidates must satisfy rigorous standards of safety and efficacy before they can be approved for sale by the U.S.
+Added: 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.
+Added: 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.
+Added: It is possible that none of the product candidates we develop will be approved for commercial sale, which would impair our ability to grow.
+Added: We have ongoing or planned nonclinical and clinical trials, including for linaclotide.
+Added: Many companies in the pharmaceutical industry have suffered significant setbacks in clinical trials even after achieving promising results in earlier nonclinical or clinical trials.
+Added: For example, in May 2020, we and AbbVie announced that our Phase II trial evaluating MD-7246, a delayed release formulation of linaclotide in adult patients with abdominal pain associated with irritable bowel syndrome with diarrhea, did not meet its primary or key secondary endpoints.
+Added: Based on these findings, we and AbbVie have discontinued development of MD-7246.
+Added: In addition, 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.
+Added: Following the assessment from an independent data monitoring committee, we unblinded the data and confirmed that IW-3718-302 did not meet the criteria, including the study’s primary endpoint of achieving a statistically significant improvement in heartburn severity.
+Added: Based on these findings, we are discontinuing development of IW-3718.
+Added: The findings from our completed nonclinical studies may not be replicated in later clinical trials, and our clinical trials may not be predictive of the results we may obtain in later-stage clinical trials or of the likelihood of regulatory approval.
+Added: Results from our clinical trials and findings from our nonclinical studies could lead to abrupt changes in our development activities, including the possible limitation or cessation of development activities associated with a particular product candidate or program.
+Added: Furthermore, our analysis of data obtained from nonclinical and clinical activities is subject to confirmation and interpretation by the U.S.
+Added: FDA and other applicable regulatory authorities, which could delay, limit or prevent regulatory approval.
+Added: FDA or other regulatory authorities also may require additional clinical trials, which may be costly or delay, limit, prevent or otherwise impact regulatory submission or approval.
+Added: Satisfaction of U.S.
+Added: FDA or other applicable regulatory requirements is costly, time-consuming, uncertain and subject to unanticipated delays.
+Added: 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.
+Added: As part of our business strategy, we may partner with pharmaceutical, biotechnology or other companies to develop and commercialize products or product candidates.
+Added: Although we have entered into such arrangements with respect to the development and commercialization of linaclotide worldwide, 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;
+Added: establish and maintain development, manufacturing, marketing, sales or distribution relationships on acceptable terms;
+Added: that such relationships, if established,
+Added: will be successful or on favorable terms;
+Added: or that we will gain market acceptance for such products or product candidates.
+Added: The process of proposing, negotiating and implementing a partnership arrangement is lengthy and complex.
+Added: If we enter into any partnering arrangements with third parties, any revenues we receive will depend upon the efforts of such third parties.
+Added: If we are unable to establish successful partnering arrangements, 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.
+Added: 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.
+Added: Delays in the completion of clinical testing could significantly affect our product development costs.
+Added: We do not know whether planned clinical trials will be completed on schedule, if at all.
+Added: The commencement and completion of clinical trials can be delayed for a number of reasons, including delays related to:
+Added: ● the ongoing COVID-19 pandemic, including restrictions on activities imposed by government authorities in response;
+Added: ● obtaining regulatory approval to commence a clinical trial;
+Added: ● reaching agreement on acceptable terms with prospective CROs and trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites;
+Added: ● manufacturing sufficient quantities of a product candidate for use in clinical trials;
+Added: ● obtaining institutional review board approval to conduct a clinical trial at a prospective site;
+Added: ● 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;
+Added: ● 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.
+Added: The COVID-19 pandemic has impacted enrollment in our clinical trials and may impact clinical trial enrollment or participation in the future, for example due to suspension of in-person procedures required for enrollment or lower or discontinued patient participation compared to pre-COVID-19 pandemic levels.
+Added: Specifically, prior to our decision to discontinue development of IW-3718, the COVID-19 pandemic impacted enrollment in our Phase III clinical trials of IW-3718 for the treatment of refractory GERD.
+Added: Clinical trials may also be delayed or discontinued as a result of ambiguous or negative interim results or assessments.
+Added: In addition, a clinical trial may be suspended or terminated by us, an institutional review board overseeing the clinical trial at a clinical trial site (with respect to that site), the U.S.
+Added: FDA, or other regulatory authorities due to a number of factors, including:
+Added: ● failure to conduct the clinical trial in accordance with regulatory requirements or the study protocols;
+Added: ● inspection of the clinical trial operations or trial sites by the U.S.
+Added: FDA or other regulatory authorities resulting in the imposition of a clinical hold;
+Added: ● unforeseen safety issues;
+Added: ● lack of adequate enrollment or funding to continue the clinical trial.
+Added: 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.
+Added: Each protocol amendment would require institutional review board review and approval, which may adversely impact the costs, timing or successful completion of the associated clinical trials.
+Added: If we or our partners terminate or experience delays in the completion of any clinical trials, the
+Added: commercial prospects for our products or product candidates may be harmed, and our ability to generate product revenues will be delayed.
+Added: 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.
+Added: Risks Related to Our Dependence on Third Parties
+Added: Because we work with partners to develop, manufacture and commercialize linaclotide, we 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.
+Added: 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 new drug application, or NDA, for LINZESS.
+Added: In addition, we are commercializing LINZESS in the U.S.
+Added: 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).
+Added: AbbVie is commercializing LINZESS in Mexico and CONSTELLA in Canada, as well as commercializing CONSTELLA in certain countries in Europe.
+Added: Astellas and AstraZeneca are responsible for development and commercialization of LINZESS in Japan and China (including Hong Kong and Macau), respectively.
+Added: 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.
+Added: We and/or our partners have commercial supply agreements with independent third parties to manufacture the linaclotide API.
+Added: 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, including those arising out of the COVID-19 pandemic, that arise in those regions.
+Added: 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.
+Added: Our linaclotide partnering strategy imposes obligations, risks and operational requirements on us as the central node in our global network of partners.
+Added: 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.
+Added: Further, we have limited ability to control the amount or timing of resources that our partners devote to linaclotide, particularly in light of the impact of the COVID-19 pandemic on our partners’ operations.
+Added: 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.
+Added: 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.
+Added: 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.
+Added: If any of our partners competes with us or assists our competitors, it could harm our competitive position.
+Added: In addition, adverse event reporting requires significant coordination with our partners and third parties.
+Added: 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, and each of Astellas, AstraZeneca and AbbVie is responsible for reporting adverse event information from its territory to us.
+Added: An AstraZeneca partner is the holder of the global safety database for lesinurad and is responsible for coordinating the safety surveillance and adverse event reporting efforts worldwide with respect to lesinurad.
+Added: If we or AstraZeneca’s partner fails to perform such activities and maintain each safety database or if such parties do not report adverse events related to such products, 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.
+Added: FDA or a foreign regulatory authority regarding such products.
+Added: Furthermore, we or such parties may fail to adequately monitor, identify or investigate adverse events, or to report adverse events to the U.S.
+Added: FDA or foreign regulatory authority accurately and within the prescribed timeframe.
+Added: If we or such parties 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 such products, removal of such products from the market, criminal prosecution, the imposition of civil monetary penalties, seizure of such products, or delay in approval of future products.
+Added: We rely entirely on contract manufacturers, our partners and other third parties to manufacture linaclotide and our other product candidates and distribute linaclotide.
+Added: 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.
+Added: We have no internal manufacturing or distribution capabilities.
+Added: Instead, we rely on a combination of contract manufacturers and our partners to manufacture API, finished drug product and finished goods for linaclotide and our other product candidates.
+Added: Each of our partners for linaclotide 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.
+Added: 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, including setbacks related to the COVID-19 pandemic described further below, our development and commercialization efforts may be materially harmed.
+Added: We and/or our partners have commercial supply agreements with independent third parties to manufacture linaclotide API.
+Added: Each of our partners and the third-party manufacturers we or our partners engage must comply with current good manufacturing practices, or GMP, and other stringent regulatory requirements enforced by the U.S.
+Added: FDA and foreign regulatory authorities in other jurisdictions.
+Added: 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.
+Added: Manufacturers of our products may be unable to comply with these GMP requirements and with other regulatory requirements.
+Added: We have little control over compliance with these regulations and standards by our partners and the third-party manufacturers we or our partners engage.
+Added: 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, including the COVID-19 pandemic.
+Added: In addition, the raw materials necessary to make API for our products and product candidates are acquired from a limited number of sources.
+Added: 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.
+Added: The manufacture of pharmaceutical products requires significant expertise and capital investment, including the development of advanced manufacturing techniques and process controls.
+Added: Manufacturers of pharmaceutical products often encounter difficulties in commercial production.
+Added: 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.
+Added: 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.
+Added: Finding alternative manufacturers or adding additional manufacturers requires a significant amount of time and involves significant expense.
+Added: 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.
+Added: 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 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.
+Added: 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.
+Added: 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.
+Added: or in the other countries where it is approved, or the ability to achieve regulatory approval, launch and commercialize linaclotide in other territories.
+Added: We work jointly and collaboratively with partners on many aspects of the development, manufacturing and/or commercialization of linaclotide.
+Added: 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.
+Added: Further, the success of our collaborations is highly dependent on the resources, efforts and skills of our partners and their key employees.
+Added: As we and our partners develop and commercialize linaclotide in the U.S.
+Added: 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.
+Added: In May 2020, AbbVie announced the completion of its acquisition of Allergan.
+Added: Our collaboration, now with AbbVie, for the development and commercialization of linaclotide in North America, and our license, now to AbbVie, to develop and commercialize linaclotide in all countries worldwide other than China (including Hong Kong and Macau) and Japan, remain in effect.
+Added: In connection with this transaction, we continue to engage with AbbVie to reestablish relationships and confirm alignment, including on our development and commercialization strategy for linaclotide.
+Added: Any failure to do so could adversely affect the development and commercialization of linaclotide.
+Added: 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.
+Added: 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.
+Added: 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.
+Added: 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.
+Added: 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 reacquire that partner’s rights with respect to linaclotide.
+Added: 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.
+Added: We have assembled a team that represents the functional areas necessary to support the commercialization of LINZESS in the U.S.
+Added: If AbbVie was subject to a change of control that allowed us to further commercialize LINZESS in the U.S.
+Added: 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.
+Added: 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.
+Added: We do not have certain operational capabilities outside of the U.S.
+Added: If AbbVie, Astellas Pharma, Inc., or Astellas, or AstraZeneca AB (together with its affiliates), 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.
+Added: 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.
+Added: In any of these situations, the development and commercialization of linaclotide could be negatively impacted.
+Added: 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 and lesinurad, expose us to product liability claims.
−Removed: If we do not successfully defend ourselves against product liability claims, we could incur substantial liabilities.
+Added: If we do not successfully defend ourselves against
+Added: product liability claims, we could incur substantial liabilities.
In addition, regardless of merit or eventual outcome, product liability claims may result in:
13 unchanged sentences
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.
−Removed: 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.
−Removed: The pharmaceutical industry and the markets in which we operate are intensely competitive.
−Removed: We compete in the marketing and sale of our products, the development of new products and the acquisition of rights to new products with commercial potential.
−Removed: Certain of our competitors have substantially greater financial, technical and human resources than us.
−Removed: 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.
−Removed: For example, in March 2019, Bausch Health Companies Inc., or Bausch Health, acquired TRULANCE (plecanatide), which, as referenced below, is a competitor to LINZESS, from Synergy Pharmaceuticals, Inc.
−Removed: Competition may also increase further as a result of advances made in
−Removed: the commercial applicability of technologies and greater availability of capital for investment in these fields.
−Removed: 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.
−Removed: These developments may render our products obsolete or noncompetitive.
−Removed: Our products compete with certain prescription therapies and over-the-counter products for the treatment of the indications for which they are approved, or their associated symptoms, and in many cases with products that have attained significant levels of market acceptance.
−Removed: The availability of prescription competitors and over-the-counter products for such conditions could limit the demand, and the price we are able to charge, for our products unless we are able to achieve market acceptance among the medical community and patients and differentiate our products on the basis of their cost and/or actual or perceived benefits.
−Removed: For example, Takeda’s AMITIZA (lubiprostone) is approved by the U.S.
−Removed: FDA for sale in the U.S.
−Removed: for the treatment of IBS-C, CIC and opioid-induced constipation, Bausch Health’s TRULANCE (plecanatide) is approved by the U.S.
−Removed: FDA for sale in the U.S.
−Removed: for the treatment of adults with IBS-C and CIC, Takeda’s MOTEGRITY (prucalopride) is approved by the U.S.
−Removed: FDA for sale in the U.S.
−Removed: for the treatment of CIC in adults, and US WorldMeds, LLC’s ZELNORM (tegaserod) is approved for sale in the U.S.
−Removed: for treatment of IBS-C in women under the age of 65.
−Removed: Over-the-counter laxatives such as MiraLAX® and DULCOLAX®, and lactulose, a prescription laxative treatment, are also available for the treatment of constipation.
−Removed: Additionally, we believe other companies are developing products which could compete with our products, should they be approved by the U.S.
−Removed: FDA or foreign regulatory authorities and become commercially available.
−Removed: For example, although not currently commercially available, the U.S.
−Removed: FDA approved Ardelyx, Inc.’s ISBRELA™ (tenapanor) for the treatment of IBS-C in adults.
−Removed: In addition, there are other compounds in late stage development and other potential competitors that are in earlier stages of development for the treatment of the indications for which our products are approved.
−Removed: If our current or potential competitors are successful in completing drug development for their drug candidates and obtain approval from the U.S.
−Removed: FDA or foreign regulatory authorities, they could limit the demand for our products.
We will incur significant liability if it is determined that we are promoting any “off-label” uses of our products.
4 unchanged sentences
FDA and other regulatory agencies do not regulate a physician’s choice of treatments, the U.S.
−Removed: FDA and other regulatory agencies do restrict manufacturer communications on off-label use.
+Added: FDA and other regulatory agencies do restrict manufacturer
+Added: 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.
9 unchanged sentences
The products that we promote are marketed in the U.S.
−Removed: and/or covered by federal healthcare programs, and, as a result, certain federal and state healthcare laws and regulations pertaining to product promotion and fraud and abuse are applicable to, and may affect, our business.
+Added: and/or covered by federal healthcare programs, and, as a result, certain federal and state healthcare laws and regulations pertaining to product promotion, fraud and abuse, privacy and price reporting and payment are applicable to, and may affect, our business.
These laws and regulations include:
−Removed: ● 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 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;
+Added: ● 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 us for reasons including providing coding and billing advice to customers;
−Removed: ● the federal Health Insurance Portability and Accountability Act of 1996, 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;
+Added: ● the federal Health Insurance Portability and Accountability Act of 1996, 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;
● 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;
−Removed: ● the so-called “federal sunshine” law, which requires pharmaceutical and medical device companies to monitor and report certain financial interactions with physicians and teaching hospitals (and additional categories of health care practitioners beginning with reports submitted in 2022) to the federal government for re-disclosure to the public;
+Added: ● the so-called “federal sunshine” law, which requires pharmaceutical and medical device companies to monitor and report certain financial interactions with physicians and teaching hospitals (and additional categories of healthcare practitioners beginning with reports submitted in 2022) to the federal government for re-disclosure to the public;
● state law equivalents of the above federal laws, such as 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, many of which differ from each other in significant ways and often are not preempted by federal laws, thus complicating compliance efforts.
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The GDPR also increases the scrutiny applied to transfers of personal data from the EEA (including from clinical trial sites in the EEA) to countries that are considered by the European Commission to lack an adequate level of data protection, such as the United States.
+Added: The July 2020 invalidation of the EU-U.S.
+Added: Privacy Shield framework also may lead to increased scrutiny on data transfers from the EEA to the United States generally and increase our costs of compliance with data privacy legislation.
In addition, we are subject to the California Consumer Privacy Act, or CCPA, which became effective on January 1, 2020.
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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.
−Removed: 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.
+Added: Any action against us for violation of these laws, rules or regulations, even if we successfully
+Added: 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.
Moreover, achieving and sustaining compliance with applicable federal and state privacy, security, fraud and reporting laws may prove costly.
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Such efforts may lead to fewer Americans having more comprehensive health insurance compliant with the ACA, even in the absence of a legislative repeal.
−Removed: For example, tax reform legislation was enacted at the end of 2017 that includes provisions to eliminate the tax penalty for individuals who do not maintain sufficient health insurance coverage beginning in 2019.
+Added: For example, tax reform legislation was enacted at the end of 2017 that eliminated the tax penalty for individuals who do not maintain sufficient health insurance coverage beginning in 2019.
The ACA has also been subject to judicial challenge.
−Removed: In December 2018, a federal district court judge, in a challenge brought by a number of state attorneys general, found the ACA unconstitutional in its entirety.
−Removed: In December 2019, a federal appeals court agreed that the individual mandate provision was unconstitutional, but remanded the case back to the district court to assess whether any provisions of the ACA were severable and could survive.
−Removed: Pending appeals, which could take some time, the ACA is still operational in all respects.
+Added: The case Texas v.
+Added: Azar, which challenges the constitutionality of the ACA, including provisions that are unrelated to healthcare reform but were enacted as part of the ACA, was argued before the Supreme Court in November 2020.
+Added: Pending resolution of the litigation, all of the ACA but the individual mandate to buy health insurance remains in effect.
+Added: Additional healthcare reform efforts have sought to address certain issues related to the COVID-19 pandemic, including an expansion of telehealth coverage under Medicare and accelerated or advanced Medicare payments to healthcare providers.
+Added: In addition, in 2020 and 2021, the U.S.
+Added: Department of Health and Human Services issued various rules that affect pricing or payment for prescription drug products.
+Added: For example, effective in 2022, revisions to 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.
+Added: Healthcare reform efforts have been and may continue to be subject to legal challenge.
+Added: For example, courts have temporarily enjoined a new “most favored nation” payment model for select drugs covered under Medicare Part B that was to take effect on January 1, 2021 and would limit
+Added: payment based on international drug price.
Adoption of new healthcare reform legislation at the federal or state level could affect demand for, or pricing of, our products or product candidates if approved for sale.
−Removed: However, we cannot predict the ultimate content, timing or effect of any healthcare reform legislation or action, or its impact on us, and healthcare reform could increase compliance costs and may adversely affect our future business and financial results.
+Added: We cannot predict, however, the ultimate content, timing or effect of any healthcare reform legislation or action, or its impact on us, and healthcare reform could increase compliance costs and may adversely affect our future business and financial results.
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.
−Removed: More broadly, 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 2029.
−Removed: Any significant spending reductions affecting Medicare, Medicaid or
−Removed: 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.
+Added: More broadly, 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 2030 (except May 1, 2020 to March 31, 2021).
+Added: 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.
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.
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FDA enhanced post- marketing authority, including the authority to require post-marketing studies and clinical trials, labeling changes based on new safety information, and compliance with risk evaluation and mitigation strategies approved by the U.S.
−Removed: We and Allergan have established a nonclinical and clinical post-marketing plan with the U.S.
+Added: 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 pediatrics.
FDA’s exercise of this authority has resulted (and is expected to continue to result) in increased development-related costs following the commercial launch of our products, and could result in potential restrictions on the sale and/or distribution of our products, even in such products’ approved indications and patient populations.
−Removed: 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.
−Removed: As part of our business strategy, we may partner with pharmaceutical, biotechnology or other companies to develop and commercialize products or product candidates.
−Removed: Although we have entered into such arrangements with respect to the development and commercialization of linaclotide worldwide, 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;
−Removed: establish and maintain development, manufacturing, marketing, sales or distribution relationships on acceptable terms;
−Removed: that such relationships, if established, will be successful or on favorable terms;
−Removed: or that we will gain market acceptance for such products or product candidates.
−Removed: The process of proposing, negotiating and implementing a partnership arrangement is lengthy and complex.
−Removed: If we enter into any partnering arrangements with third parties, any revenues we receive will depend upon the efforts of such third parties.
−Removed: If we are unable to establish successful partnering arrangements, 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.
−Removed: In pursuing our growth strategy, we will incur a variety of costs and may devote resources to potential opportunities that are never completed or for which we never receive the benefit.
−Removed: Our failure to successfully acquire, develop and market additional product candidates or approved products would impair our ability to grow and/or adversely affect our business.
−Removed: As part of our growth strategy, we intend to explore further linaclotide development opportunities.
−Removed: We and Allergan 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.
−Removed: These development efforts may fail or may not increase the revenues that we generate from LINZESS.
−Removed: 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 U.S.
−Removed: FDA or in other countries or harm linaclotide’s reputation in the marketplace, each of which could materially harm our revenues from linaclotide.
−Removed: We are also pursuing various other programs in our pipeline, including MD-7246, a delayed release form of linaclotide that is being developed as an oral, intestinal, non-opioid, pain relieving agent for patients suffering from abdominal pain associated with certain GI diseases, the potential treatment of IBS-D, and IW-3718, a gastric retentive formulation of a bile acid sequestrant for the potential treatment of persistent gastroesophageal reflux disease, and the strength of our company’s pipeline will depend in large part on the outcomes of these studies.
−Removed: We may spend several
−Removed: years and make significant investments in developing any current or future internal product candidate, and failure may occur at any point.
−Removed: Our product candidates are in various stages of development and must satisfy rigorous standards of safety and efficacy before they can be approved for sale by the U.S.
−Removed: To satisfy these standards, we must allocate resources among our various development programs and we must engage in costly and lengthy research and development efforts, which are subject to unanticipated delays and other significant uncertainties.
−Removed: 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.
−Removed: It is possible that none of the product candidates we are developing will be approved for commercial sale, which would impair our ability to grow.
−Removed: We have ongoing or planned nonclinical and clinical trials for linaclotide and our product candidates, including MD-7246 and IW-3718.
−Removed: Many companies in the pharmaceutical industry have suffered significant setbacks in clinical trials even after achieving promising results in earlier nonclinical or clinical trials.
−Removed: The findings from our completed nonclinical studies may not be replicated in later clinical trials, and our clinical trials may not be predictive of the results we may obtain in later-stage clinical trials or of the likelihood of regulatory approval.
−Removed: Results from our clinical trials and findings from our nonclinical studies could lead to abrupt changes in our development activities, including the possible limitation or cessation of development activities associated with a particular product candidate or program.
−Removed: Furthermore, our analysis of data obtained from nonclinical and clinical activities is subject to confirmation and interpretation by the U.S.
−Removed: FDA and other applicable regulatory authorities, which could delay, limit or prevent regulatory approval.
−Removed: Satisfaction of U.S.
−Removed: FDA or other applicable regulatory requirements is costly, time-consuming, uncertain and subject to unanticipated delays.
−Removed: In addition, because our internal research capabilities are limited, we may be dependent upon pharmaceutical and biotechnology companies, academic scientists and other researchers to sell or license products or technology to us.
−Removed: The success of this strategy depends partly upon our ability to identify, select and acquire promising pharmaceutical product candidates and products.
−Removed: The process of proposing, negotiating and implementing a license or acquisition of a product candidate or approved product is lengthy and complex.
−Removed: Other companies, including some with substantially greater financial, marketing and sales resources, may compete with us for the license or acquisition of product candidates and approved products.
−Removed: We have limited resources to identify and execute the acquisition or in-licensing of third-party products, businesses and technologies and integrate them into our current infrastructure.
−Removed: Moreover, we may 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.
−Removed: We may not be able to acquire the rights to additional products or product candidates on terms that we find acceptable, or at all.
−Removed: In addition, such acquisitions may entail numerous operational and financial risks, including:
−Removed: ● exposure to unknown liabilities;
−Removed: ● disruption of our business and diversion of our management’s time and attention to develop acquired products, product candidates or technologies;
−Removed: ● incurrence of substantial debt, dilutive issuances of securities or depletion of cash to pay for acquisitions;
−Removed: ● higher than expected acquisition and integration costs;
−Removed: ● difficulty in combining the operations and personnel of any acquired businesses with our operations and personnel;
−Removed: ● increased amortization expenses;
−Removed: ● impairment of relationships with key suppliers or customers of any acquired businesses due to changes in management and ownership;
−Removed: ● inability to motivate key employees of any acquired businesses.
−Removed: 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.
−Removed: 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.
−Removed: Also, any product candidate that we acquire may require additional development efforts prior to commercial sale,
−Removed: including extensive clinical testing and approval by the U.S.
−Removed: FDA and applicable foreign regulatory authorities.
−Removed: 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.
−Removed: Delays in the completion of clinical testing of any of our product candidates could result in increased costs and delay or limit our ability to generate revenues.
−Removed: Delays in the completion of clinical testing could significantly affect our product development costs.
−Removed: We do not know whether planned clinical trials will be completed on schedule, if at all.
−Removed: The commencement and completion of clinical trials can be delayed for a number of reasons, including delays related to:
−Removed: ● obtaining regulatory approval to commence a clinical trial;
−Removed: ● reaching agreement on acceptable terms with prospective clinical 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;
−Removed: ● manufacturing sufficient quantities of a product candidate for use in clinical trials;
−Removed: ● obtaining institutional review board approval to conduct a clinical trial at a prospective site;
−Removed: ● 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;
−Removed: ● 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.
−Removed: Clinical trials may also be delayed or discontinued as a result of ambiguous or negative interim results.
−Removed: In addition, a clinical trial may be suspended or terminated by us, an institutional review board overseeing the clinical trial at a clinical trial site (with respect to that site), the U.S.
−Removed: FDA, or other regulatory authorities due to a number of factors, including:
−Removed: ● failure to conduct the clinical trial in accordance with regulatory requirements or the study protocols;
−Removed: ● inspection of the clinical trial operations or trial sites by the U.S.
−Removed: FDA or other regulatory authorities resulting in the imposition of a clinical hold;
−Removed: ● unforeseen safety issues;
−Removed: ● lack of adequate enrollment or funding to continue the clinical trial.
−Removed: Additionally, changes in regulatory requirements and guidance may occur, and we may need to amend clinical trial protocols to reflect these changes.
−Removed: Each protocol amendment would require institutional review board review and approval, which may adversely impact the costs, timing or successful completion of the associated clinical trials.
−Removed: If we or our partners terminate or experience delays in the completion of any clinical trials, the commercial prospects for our product candidates may be harmed, and our ability to generate product revenues will be delayed.
−Removed: 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.
+Added: Risks Related to the Separation of Cyclerion
We may incur operational difficulties or be exposed to claims and liabilities as a result of the separation of Cyclerion.
−Removed: On April 1, 2019, we distributed all of the outstanding shares of Cyclerion Therapeutics, Inc., or Cyclerion, common stock to Ironwood stockholders in connection with the separation of our s oluble guanylate cyclase business, or the Separation.
+Added: On April 1, 2019, we distributed all of the outstanding shares of Cyclerion Therapeutics, Inc., or Cyclerion, common stock to Ironwood stockholders in connection with the separation of our soluble guanylate cyclase business, or the Separation.
In connection with the distribution, we entered into a separation agreement and various other agreements (including a tax matters agreement, an employee matters agreement, transition services agreements, an intellectual property license agreement and a development agreement).
−Removed: These agreements govern the separation and distribution and
−Removed: the relationship between us and Cyclerion going forward, including with respect to potential tax-related losses associated with the separation and distribution.
−Removed: They also provide for the performance of services by each company for the benefit of the other for a period of time.
+Added: These agreements govern the separation and distribution and the relationship between us and Cyclerion going forward, including with respect to potential tax-related losses associated with the separation and distribution.
+Added: In addition, the development agreement provides for the performance of services by Cyclerion for our benefit for a period of time.
If Cyclerion is unable to satisfy its obligations under these agreements, we could incur losses or operational challenges or difficulties and may not have sufficient resources available for such services.
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In addition, we are smaller and less diversified, with a narrower business focus, than we were before the Separation and therefore may be more vulnerable to changing market conditions.
−Removed: The Separation also presents a number of significant risks to our internal processes, including the failure to maintain an adequate control environment due to changes to our infrastructure technology systems and financial reporting processes.
−Removed: 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 and motivate key personnel.
−Removed: We may not be able to attract or motivate 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.
−Removed: If we are not able to attract and motivate necessary personnel to accomplish our business objectives, we will experience constraints that will significantly impede the achievement of our objectives.
−Removed: We are highly dependent on the drug research, development, regulatory, commercial, financial and other expertise of our management, particularly Mark Mallon, our chief executive officer;
−Removed: Gina Consylman, our senior vice president, chief financial officer, and treasurer;
−Removed: and Thomas A.
−Removed: McCourt, our president.
−Removed: Transitions in our senior management team and other key employees may result in operational disruptions, and our business may be harmed as a result.
−Removed: In addition to the competition for personnel, the Boston area in particular is characterized by a high cost of living.
−Removed: 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.
−Removed: 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.
−Removed: 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 have arrangements with other companies to assist in the development and commercialization of products that may compete with ours.
−Removed: 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.
−Removed: 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.
−Removed: We also rely to a large extent on information technology systems to operate our business, including to deliver our products.
−Removed: 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.
−Removed: Similarly, our business partners and other third-party providers possess certain of our sensitive data.
−Removed: The secure maintenance of this information is critical to our operations and business strategy.
−Removed: Despite our security measures, our large and complex information technology and infrastructure (and those of our partners, vendors and third-party providers) may be vulnerable to attacks by hackers or breached due to employee error, malfeasance or other disruptions.
−Removed: 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.
−Removed: 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.
−Removed: Any such interruptions or breach would substantially impair our ability to operate our business and would compromise our, and their, networks and the information stored there could be accessed, publicly disclosed, lost or stolen.
−Removed: 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, and damage our reputation, any of which could adversely affect our business.
−Removed: While we maintain cyber liability insurance, this insurance may not be sufficient to cover the losses that may result from an interruption or breach of our (or our partners’, vendors’ and third-party providers’) systems.
−Removed: Our business could be negatively affected as a result of a proxy contest or certain other stockholder actions.
−Removed: 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.
−Removed: 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.
−Removed: In addition, a proxy contest would require us to incur significant costs, including legal fees and proxy solicitation expenses.
Risks Related to Intellectual Property
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We have several issued patents in the U.S.
−Removed: related to LINZESS (linaclotide), including a LINZESS composition of matter and methods of use patent (U.S.
+Added: 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.
−Removed: patents related to LINZESS include multiple patents relating to our commercial, room temperature stable formulation of the 145 mcg and 290 mcg doses of linaclotide and methods of using this formulation, the latest of which expires in the early 2030s, as well as other patents covering processes for making LINZESS, formulations thereof, and molecules related to LINZESS.
+Added: patents related to LINZESS include multiple patents relating to our commercial, room temperature stable formulations of the 72 mcg, 145 mcg and 290 mcg
+Added: doses of linaclotide and methods of using these formulations, the latest of which expires in the early 2030s, as well as other patents covering processes for making LINZESS, formulations thereof, and molecules related to LINZESS.
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 U.S.
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In addition, we have several pending patent applications in the U.S.
−Removed: For example, we are pursuing patent applications that cover the commercial formulation of the 72 mcg dose of LINZESS.
We believe in the strength of our LINZESS patent portfolio and that we have sufficient freedom to operate;
−Removed: however, if any of our present or future patents is invalidated, or our pending patent applications are not granted, our ability to prevent third parties from competing with LINZESS could be limited and our business and financial results may be materially harmed.
+Added: 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 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.
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Moreover, the U.S.
−Removed: Supreme Court has ruled on several patent cases in recent years, narrowing the scope of patent protection available and weakening the rights of patent owners in certain circumstances.
+Added: 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.
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A license may not be available to us on acceptable terms, if at all.
−Removed: In addition, during litigation, the counter-party 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.
+Added: 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.
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FDA regulations.
−Removed: 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
−Removed: commercialize generic versions of one or more LINZESS doses.
+Added: 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.
−Removed: We and Allergan have received Paragraph IV certification notice letters, or Notice Letters, regarding ANDAs submitted to the U.S.
+Added: 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.
−Removed: For additional information relating to such ANDAs, see Item 3, Legal Proceedings , elsewhere in this Annual Report on Form 10-K .
+Added: In the past, we have filed patent infringement lawsuits against five companies making such ANDA filings, and we have entered into settlement agreements dismissing the lawsuits with each company that has made ANDA filings.
Frequently, innovators receive multiple ANDA filings.
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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.
−Removed: In the past, we have filed patent infringement lawsuits against five companies making such ANDA filings, and we have entered into settlement agreements dismissing the lawsuits with each company that has made ANDA filings.
−Removed: For additional information relating to such lawsuits and settlements, see Item 3, Legal Proceedings , elsewhere in this Annual Report on Form 10-K .
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.
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We have financed our business to date primarily through the issuance of equity, our collaboration and license arrangements, and debt issuances, including our June 2015 issuance of our 2.25% Convertible Senior Notes due June 15, 2022, or the 2022 Convertible Notes, and our August 2019 issuance of our 0.75% Convertible Senior Notes due 2024, or the 2024 Convertible Notes, and our 1.50% Convertible Senior Notes due 2026, or the 2026 Convertible Notes (together with the 2022 Convertible Notes and the 2024 Convertible Notes, the Convertible Senior Notes).
−Removed: We currently derive a significant portion of our revenue from our LINZESS collaboration with Allergan for the U.S.
+Added: 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.
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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.
−Removed: Additionally, our sale of API outside of the U.S.
−Removed: has fluctuated in the past and will significantly decrease beginning in 2020.
−Removed: Under the terms of our amended and restated agreements with both Astellas and AstraZeneca, entered into in August 2019 and September 2019, respectively, we will no longer be responsible for the supply of linaclotide API to Astellas or AstraZeneca beginning in 2020.
Prior to the year ended December 31, 2019, we incurred net losses in each year since our inception in 1998.
−Removed: For the year ended December 31, 2019, we recorded net income of approximately $21.5 million.
−Removed: We incurred net losses of approximately $282.4 million and approximately $116.9 million for the years ended December 31, 2018 and 2017, respectively.
As of December 31, 2020, we had an accumulated deficit of approximately $1.5 billion.
−Removed: 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.
+Added: 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, particularly in light of the negative financial impact that the COVID-19 pandemic may have on our business in the future.
Further, we expect to continue to incur substantial expenses in connection with our efforts to commercialize linaclotide and research and develop our 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.
−Removed: Failure to achieve sustainable net income and positive cash flows would have an adverse effect on stockholders’ equity and working capital.
−Removed: We may need additional funding and may be unable to raise capital when needed, which could cause us to delay, reduce or eliminate our product development programs or commercialization efforts.
−Removed: We have previously raised funds to finance our operations through capital raising activities, including the sale of shares of our common stock in public offerings and convertible and other debt issuances.
+Added: Failure to achieve sustainable net income and maintain positive cash flows would have an adverse effect on stockholders’ equity and working capital.
+Added: 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.
+Added: 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 primary care drugs, purchasing commercial quantities of pharmaceutical products, developing product candidates, conducting clinical trials and accessing externally developed products are expensive and uncertain.
5 unchanged sentences
● the regulatory approval of linaclotide within new indications, populations and formulations, as well as the associated development and commercial milestones and royalties;
−Removed: ● the rate of progress, the cost of our clinical trials and the other costs associated with our linaclotide product development programs, including our 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;
+Added: ● the rate of progress, the cost of our clinical trials and the other costs associated with our development programs, including our 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;
3 unchanged sentences
● whether the holders of our Convertible Senior Notes hold the notes to maturity without conversion into our Class A Common Stock 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;
−Removed: ● whether we seek to 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
+Added: ● 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.
−Removed: Our ability to pay principal of and interest on our outstanding debt securities will depend in part on the receipt of payments from Allergan under our collaboration agreement for North America.
+Added: Our ability to pay principal of and interest on our outstanding debt securities will depend in part on the receipt of payments from AbbVie under our collaboration agreement for North America.
In June 2015, we issued approximately $335.7 million aggregate principal amount of our 2022 Convertible Notes bearing an annual interest rate of 2.25%.
−Removed: In August 2019, we issued $200.0 million aggregate principal amount of our 2024 Convertible Notes bearing an annual interest rate of 0.75% and $200.0 million aggregate principal amount of our 2026 Convertible Notes bearing an annual interest rate of 1.50%, and we used a portion of the proceeds from this offering to repurchase $215.0 million aggregate principal amount of the 2022 Convertible Notes.
+Added: In August 2019, we issued $200.0 million aggregate principal amount of our 2024 Convertible Notes bearing an annual interest rate of 0.75% and $200.0 million aggregate principal amount of
+Added: our 2026 Convertible Notes bearing an annual interest rate of 1.50%, and we used a portion of the proceeds from this offering to repurchase $215.0 million aggregate principal amount of the 2022 Convertible Notes.
Semi-annual payments on our 2022 Convertible Notes began on December 15, 2015 and semi-annual payments on each of our 2024 Convertible Notes and 2026 Convertible Notes began on December 15, 2019.
−Removed: We expect that for the next few years, at a minimum, the net quarterly payments from Allergan will be a significant source of cash flows from operations.
−Removed: If the cash flows derived from the net quarterly payments that we receive from Allergan 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.
−Removed: The determination of whether Allergan 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.
−Removed: as well as the development, manufacturing and commercialization expenses incurred by each of us and Allergan under the collaboration agreement for North America.
−Removed: Accordingly, since we cannot guarantee that our company will maintain net income or generate and maintain positive cash flows, we cannot provide assurances 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 Allergan, (ii) there will be a net quarterly payment from Allergan at all or (iii) we will not also be required to make a true-up payment to Allergan under the collaboration agreement for North America, in each case, in respect of a particular quarterly period.
+Added: 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.
+Added: 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.
+Added: 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.
+Added: as well as the development, manufacturing and commercialization expenses incurred by each of us and AbbVie under the collaboration agreement for North America.
+Added: Accordingly, since we cannot guarantee that our company will maintain net income or positive cash flows, we cannot provide assurances 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, in each case, in respect of a particular quarterly period.
Our indebtedness could adversely affect our financial condition or restrict our future operations.
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In addition, while none of the indentures governing our Convertible Senior Notes includes covenants restricting the operation of our business except in certain limited circumstances, in the event of a default under any of the Convertible Senior Notes, the applicable noteholders or the trustee under the indenture governing the applicable Convertible Senior Notes may accelerate our payment obligations under such Convertible Senior Notes, which could have a material adverse effect on our business, financial condition and results of operations.
−Removed: 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 common stock listed on The Nasdaq Global or Global Select Market or The New York Stock Exchange), subject to the terms of each of the indenture governing the Convertible Senior Notes.
+Added: 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
+Added: Class A Common Stock listed on The Nasdaq Global or Global Select Market or The New York Stock Exchange), subject to the terms of each 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.
3 unchanged sentences
In connection with the issuance of our 2022 Convertible Notes, we entered into convertible note hedge transactions, or the Convertible Note Hedges, and separate note hedge warrant transactions, or the Note Hedge Warrants, with certain financial institutions.
−Removed: The Convertible Note Hedges and Note Hedge Warrants were partially terminated in
−Removed: connection with the repurchase of $215.0 million aggregate principal amount of the 2022 Convertible Notes in August 2019.
+Added: The Convertible Note Hedges and Note Hedge Warrants were partially terminated in connection with the repurchase of $215.0 million aggregate principal amount of the 2022 Convertible Notes in August 2019.
Additionally, in connection with the issuance of our 2024 Convertible Notes and our 2026 Convertible Notes, we entered into capped call transactions, or the Capped Calls, with certain financial institutions.
13 unchanged sentences
● our execution of any collaboration, partnership, licensing or other strategic arrangements, and the timing of payments we may make or receive under these arrangements;
−Removed: ● any excess or obsolete inventory or impairments of assets or goodwill, and associated write-downs;
+Added: ● any impairments of assets or goodwill, and associated write-downs;
● any variations in the level of expenses related to our development programs;
2 unchanged sentences
● any material lawsuit in which we may become involved;
+Added: ● the impact of the COVID-19 pandemic or other public health epidemics, 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.
6 unchanged sentences
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.
+Added: 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.
−Removed: Risks Related to Securities Markets and Investment in Our Stock
+Added: General Risk Factors
+Added: Public health emergencies, epidemics, or pandemics, such as the COVID-19 pandemic, impact our business.
+Added: In December 2019, a novel strain of coronavirus (COVID-19) emerged in Wuhan, Hubei Province, China.
+Added: On March 11, 2020, the World Health Organization declared a global pandemic and recommended containment and mitigation measures worldwide.
+Added: On March 13, 2020, former U.S.
+Added: President Donald Trump announced a national emergency relating to the pandemic.
+Added: Government authorities in the U.S.
+Added: have recommended or imposed various containment and mitigation measures on large portions of the population, and similar measures have also been taken in many other countries around the world.
+Added: Both the outbreak of COVID-19 and the containment and mitigation efforts have a serious adverse impact on the U.S.
+Added: economy and the economies of other countries around the world, the severity and duration of which are uncertain.
+Added: Government stabilization efforts will only partially mitigate the consequences.
+Added: The COVID-19 pandemic has impacted, and is expected to continue to impact, our business and operations in a number of ways and there are significant uncertainties surrounding the extent and duration of such impacts.
+Added: Factors that will influence the impact on our business and operations include the duration and extent of the outbreak, the duration and extent of imposed or recommended containment and mitigation measures, and the general economic consequences of the pandemic.
+Added: Addressing the impacts of the COVID-19 pandemic has, and likely will for an extended period, required significant time and has diverted the attention of our management, other employees and our board of directors.
+Added: The increase in virtual customer support and limitations on customer access by our customer-facing employees that was prompted by the COVID-19 pandemic contributed to our decision to make virtual promotion a more permanent component of our overall selling model and may further change our commercial model or the market strategy in the industry.
+Added: Should we be unable to evolve with any changes in the commercial landscape, we may be unable to maintain or grow our revenues from the commercialization of LINZESS or successfully commercialize future products.
+Added: In addition, changes in insurance coverage or reimbursement levels by governmental authorities, private health insurers and other third-party payors, or changes in the type of such coverage held by patients (including changes from commercial insurance to Medicaid) or the loss of coverage by some patients, due to the impacts of the COVID-19 pandemic (including the related increase in unemployment in the U.S.) may negatively impact our revenue from LINZESS.
+Added: Moreover, continuing impacts to healthcare access or administration (including, for example, limitations on medications or procedures deemed “non-essential” and reduced interaction between patients and physicians) due to the COVID-19 pandemic may impact demand for LINZESS and materially harm our business and commercialization efforts.
+Added: Most of our customer-facing employees are engaged in in-person work practices;
+Added: however, they are limited in the number of in-person details they are able to conduct due to containment and mitigation measures related to the COVID-19 pandemic.
+Added: We monitor the impact of the COVID-19 pandemic in the territories where our customer-facing employees are engaged in in-person work practices, and in some cases, we have paused or delayed in-person work practices as a result of the impact of the COVID-19 pandemic in those territories, and may do so again in the future.
+Added: Customer-facing employees who are not providing in-person services continue to support their customers virtually through telephone and web-based technologies.
+Added: Headquarters employees are expected to have the option to work remotely through mid-2021.
+Added: We may delay, stop or otherwise limit in-person work in the future pending relevant health authority guidance and additional safety or other considerations.
+Added: If our employees are unable to work from home effectively, or if the COVID-19 pandemic otherwise impacts employees’ ability to work, for example due to containment and mitigation measures related to the COVID-19 pandemic, illness, lack of resources or inadequate technology, or restrictions, closures or other limits on school and other childcare options, our business will be materially harmed .
+Added: Specifically, new or continuing limits on the ability of our customer-facing employees to meet with physicians and patients to visit healthcare providers and pharmacists (including due to continued or future remote working arrangements, containment and mitigation measures that limit access to customers or other restrictions related to the COVID-19 pandemic) may have an extended negative impact on LINZESS sales.
+Added: Revenue from LINZESS sales or the progression of our trials will be affected should the COVID-19 pandemic cause significant disruptions to manufacturing operations or supply of LINZESS to the U.S.
+Added: or API, finished drug product or finished goods for linaclotide or our product candidates , for example due to impacts of the COVID-19 pandemic on personnel involved in the manufacturing and supply chain, international travel and shipping restrictions, inability of vendors to provide services, closed manufacturing sites, or any other disruptions in the international supply chain.
+Added: In addition, the COVID-19 pandemic has impacted enrollment in our clinical trials, and may impact clinical trial enrollment or participation in the future, for example due to suspension of in-person procedures required for enrollment or lower or discontinued patient participation compared to pre-COVID-19 pandemic levels.
+Added: Specifically, prior to our decision to discontinue development of IW-3718, the COVID-19 pandemic impacted enrollment in our Phase III clinical trials of IW-3718 for the treatment of refractory gastroesophageal reflex disease, or refractory GERD.
+Added: In addition, the progression of our pipeline could be impacted should any of our key vendors, including clinical research organizations, or CROs, and other clinical vendors, be unable to provide timely or sufficient services due to the impact of the COVID- 19 pandemic.
+Added: The spread of COVID-19 continues to disrupt the U.S.
+Added: healthcare and healthcare regulatory system.
+Added: Capital markets in the U.S.
+Added: and around the world have also been negatively impacted, which may harm our business, including our ability to obtain future financing.
+Added: The COVID-19 pandemic, including containment and mitigation measures, has impacted our business and operations, and could have a material adverse impact on our financial condition and results of operations in the future, including for an extended period of time.
+Added: 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.
+Added: 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.
+Added: 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.
+Added: We are highly dependent on the drug research, development, regulatory, commercial, financial and other expertise of our management, particularly Mark Mallon, our chief executive officer;
+Added: Gina Consylman, our senior vice president, chief financial officer, and treasurer;
+Added: McCourt, our president;
+Added: Jason Rickard, our senior vice president and chief operating officer and Michael Shetzline, our senior vice president, chief medical officer and head of drug development.
+Added: On February 4, 2021, Mr.
+Added: Mallon notified us that he is resigning his position as chief executive officer and a member of our company’s board of directors, in each case effective March 12, 2021.
+Added: Effective upon Mr.
+Added: Mallon’s departure, Mr.
+Added: McCourt will serve as our interim chief executive officer while the Board conducts a candidate search for Mr.
+Added: Mallon’s permanent successor.
+Added: This and any additional transitions in our senior management team or other key employees, or the unavailability of any such persons for any reason (including due to the COVID-19 pandemic), 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.
+Added: Further, if we are unable to attract a qualified candidate to become our permanent chief executive officer in a timely manner, our business and prospects may be adversely affected.
+Added: In addition to the competition for personnel, the Boston area in particular is characterized by a high cost of living.
+Added: 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.
+Added: 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.
+Added: 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 have arrangements with other companies to assist in the development and commercialization of products that may compete with ours.
+Added: 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.
+Added: 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.
+Added: We also rely to a large extent on information technology systems to operate our business, including to deliver our products.
+Added: 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.
+Added: Similarly, our business partners and other third-party providers possess certain of our sensitive data.
+Added: The secure maintenance of this information is critical to our operations and business strategy.
+Added: Despite our security measures, our large and complex information technology and infrastructure (and those of our partners, vendors and third-party providers) may be vulnerable to attacks by hackers or breached due to employee, partner, vendor or third-party error, malfeasance or other disruptions.
+Added: 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.
+Added: 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.
+Added: Further, while some or all of our workforce, and those of our partners, vendors and other third-party providers, work remotely as a result of the COVID-19 pandemic or otherwise, we may have greater vulnerability to cyberattacks or other losses of confidential information, as well as interruptions in information technology systems.
+Added: 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.
+Added: Any such access, disclosure or other loss of information could result
+Added: 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.
+Added: 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.
4 unchanged sentences
At our 2019 annual meeting of stockholders, our stockholders approved an amendment to our certificate of incorporation to declassify our board of directors to allow our stockholders to vote on the election of the entire board of directors on an annual basis, rather than on a staggered basis.
−Removed: This declassification will be phased in such that, once completed in 2022, stockholders will have the opportunity to replace the entire board at a single stockholders’ meeting.
+Added: This declassification is being phased in such that, once completed in 2022, stockholders will have the opportunity to replace the entire board at a single stockholders’ meeting and at each annual stockholders’ meeting thereafter.
As required by Delaware law, the amendment to our certificate of incorporation also reflects that, once the board of directors is declassified, stockholders may remove directors with or without cause.
4 unchanged sentences
Furthermore, as described above, until our board of directors is declassified, stockholders may only remove a member of our board of directors for cause.
−Removed: These provisions may discourage or deter a potential acquirer from conducting a
−Removed: solicitation of proxies to elect such acquirer’s own slate of directors or otherwise attempting to obtain control of our company.
+Added: 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.
15 unchanged sentences
Our net profit or net loss generated from the sales of LINZESS in the U.S.
−Removed: is partially determined based on amounts provided by Allergan and involves the use of estimates and judgments, which could be modified in the future.
−Removed: 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 Allergan for the U.S., the costs incurred in developing and commercializing it in order to accurately report our results of operations.
+Added: is partially determined based on amounts provided by AbbVie and involves the use of estimates and judgments, which could be modified in the future.
+Added: 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.
10 unchanged sentences
● announcements of the introduction of new products by us or our competitors;
−Removed: ● announcements concerning product development results, including clinical trial results, or intellectual property rights of us or others;
+Added: ● 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;
4 unchanged sentences
● discussion of us or our stock price in the financial or scientific press or in online investor communities;
+Added: ● the impact of the COVID-19 pandemic or other public health epidemics, including containment or mitigation measures, or natural disasters.
+Added: Our business could be negatively affected as a result of a proxy contest or certain other stockholder actions.
+Added: 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.
+Added: 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.
+Added: 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.
4 unchanged sentences
We believe that our facilities are suitable and adequate for our needs for the foreseeable future.
+Added: Legal Proceedings
+Added: Mine Safety Disclosures
+Added: Not applicable.
Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.