Insmed
Annual Report 2018

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Morningstar® Document Research℠ FORM 10-KINSMED INC - INSMFiled: February 22, 2019 (period: December 31, 2018)Annual report with a comprehensive overview of the companyThe information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The userassumes all risks for any damages or losses arising from any use of this information, except to the extent such damages or losses cannot belimited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsUNITED STATESSECURITIES AND EXCHANGE COMMISSIONWashington, D.C. 20549FORM 10-K(Mark One) ý ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934For the fiscal year ended December 31, 2018ORo TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934For the transition period from to Commission File Number 0-30739INSMED INCORPORATED(Exact name of registrant as specified in its charter)Virginia(State or other jurisdiction of incorporation ororganization) 54-1972729(I.R.S. employer identification no.) 10 Finderne Avenue, Building 10Bridgewater, New Jersey 08807(Address of principal executive offices) (908) 977-9900(Registrant's telephone number including area code)Securities registered pursuant to Section 12(b) of the Act:Title of each class Name of each exchange on whichregisteredCommon Stock, par value $0.01 per share Nasdaq Global Select MarketSecurities registered pursuant to Section 12(g) of the Act: NoneIndicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes [ü] No [ ]Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes [ ] No [ü]Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes [ü] No [ ]Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§ 232.405 ofthis chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes [ü] No [ ]Indicate by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K is not contained herein, and will not be contained, to the best of registrant'sknowledge, in definitive proxy or information statements incorporated by reference in Part III of this Form 10-K or any amendment to this Form 10-K. [ ]Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company(See the definitions of "large accelerated filer," "accelerated filer," "smaller reporting company" and "emerging growth company" in Rule 12b-2 of the Exchange Act). Largeaccelerated filer [ü] Accelerated filer [ ] Non-accelerated filer [ ] Smaller reporting company [ ] Emerging growth company [ ]If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financialaccounting standards provided pursuant to Section 13(a) of the Exchange Act [ ]Indicate by check mark whether the registrant is a Shell Company (as defined in Rule 12b-2 of the Exchange Act). Yes [ ] No [ü]The aggregate market value of the voting and non-voting common equity held by non-affiliates of the registrant on June 30, 2018, was $1,803 million (based on the closing price forshares of the registrant's common stock as reported on the Nasdaq Global Select Market on that date). In determining this figure, the registrant has assumed solely for this purpose thatall of its directors, executive officers, persons beneficially owning 10% or more of the registrant's outstanding common stock and certain other stockholders of the registrant may beconsidered to be affiliates. This assumption shall not be deemed conclusive as to affiliate status for this or any other purpose.On February 15, 2019, there were 77,538,562 shares of the registrant's common stock, $0.01 par value, outstanding.____________________________________________________________________________Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsDOCUMENTS INCORPORATED BY REFERENCEPortions of the registrant's definitive Proxy Statement for its 2019 Annual Meeting of Shareholders to be filed with the Securities and Exchange Commission no laterthan April 30, 2019 and to be delivered to shareholders in connection with the 2019 Annual Meeting of Shareholders, are herein incorporated by reference in Part III of this Form 10-K.Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDINDEX PAGEREPORT:FORM 10-K CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS4PART I 6 ITEM 1BUSINESS6 ITEM 1ARISK FACTORS28 ITEM 1BUNRESOLVED STAFF COMMENTS49 ITEM 2PROPERTIES50 ITEM 3LEGAL PROCEEDINGS50 ITEM 4MINE SAFETY DISCLOSURES50PART II 51 ITEM 5MARKET FOR REGISTRANT'S COMMON EQUITY, RELATED STOCKHOLDERMATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES51 ITEM 6SELECTED FINANCIAL DATA52 ITEM 7MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION ANDRESULTS OF OPERATIONS54 ITEM 7AQUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK66 ITEM 8FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA66 ITEM 9CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING ANDFINANCIAL DISCLOSURE67 ITEM 9ACONTROLS AND PROCEDURES67 ITEM 9BOTHER INFORMATION68PART III 69 ITEM 10DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE69 ITEM 11EXECUTIVE COMPENSATION69 ITEM 12SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENTAND RELATED STOCKHOLDER MATTERS69 ITEM 13CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS AND DIRECTORINDEPENDENCE69 ITEM 14PRINCIPAL ACCOUNTANT FEES AND SERVICES69PART IV 70 ITEM 15EXHIBITS AND FINANCIAL STATEMENT SCHEDULES70 ITEM 16FORM 10-K SUMMARY73REPORTS OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM75CONSOLIDATED FINANCIAL STATEMENTS77Unless the context otherwise indicates, references in this Form 10-K to “Insmed Incorporated” refers to Insmed Incorporated, a Virginia corporation, and“Company,” “Insmed,” “we,” “us” and “our” refer to Insmed Incorporated together with its consolidated subsidiaries. INSMED, CONVERT and ARIKAYCEare trademarks of Insmed Incorporated. This Form 10-K also contains trademarks of third parties. Each trademark of another company appearing in thisForm 10-K is the property of its owner.3Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsCAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS This Annual Report on Form 10-K contains forward-looking statements that involve substantial risks and uncertainties. "Forward-lookingstatements," as that term is defined in the Private Securities Litigation Reform Act of 1995, are statements that are not historical facts and involve a numberof risks and uncertainties. Words herein such as "may," "will," "should," "could," "would," "expects," "plans," "anticipates," "believes," "estimates," "projects,""predicts," "intends," "potential," "continues," and similar expressions (as well as other words or expressions referencing future events, conditions orcircumstances) identify forward-looking statements. Forward-looking statements are based on our current expectations and beliefs, and involve known and unknown risks, uncertainties and otherfactors, which may cause our actual results, performance and achievements and the timing of certain events to differ materially from the results,performance, achievements or timing discussed, projected, anticipated or indicated in any forward-looking statements. Such risks, uncertainties and otherfactors include, among others, the following:•failure to successfully commercialize or maintain US approval for ARIKAYCE® (amikacin liposome inhalation suspension), our only approvedproduct;•uncertainties in the degree of market acceptance of ARIKAYCE by physicians, patients, third-party payors and others in the health-carecommunity;•our inability to obtain full approval of ARIKAYCE from the US Food and Drug Administration (FDA), including the risk that we will notsuccessfully complete the confirmatory post-marketing study required for full approval;•inability of us, PARI Pharma GmbH (PARI) or our third-party manufacturers to comply with regulatory requirements related to ARIKAYCE or theLamira Nebulizer System (Lamira);•our inability to obtain adequate reimbursement from government or third-party payors for ARIKAYCE or acceptable prices for ARIKAYCE;•development of unexpected safety or efficacy concerns related to ARIKAYCE;•inaccuracies in our estimates of the size of the potential markets for ARIKAYCE or in data we have used to identify physicians;•our inability to create an effective direct sales and marketing infrastructure or to partner with third parties that offer such an infrastructure fordistribution of ARIKAYCE;•failure to obtain regulatory approval to expand ARIKAYCE’s indication to a broader patient population;•failure to successfully conduct future clinical trials for ARIKAYCE and our product candidates, including due to our limited experience inconducting preclinical development activities and clinical trials necessary for regulatory approval and our inability to enroll or retain sufficientpatients to conduct and complete the trials or generate data necessary for regulatory approval;•risks that our clinical studies will be delayed or that serious side effects will be identified during drug development;•failure to obtain regulatory approvals for ARIKAYCE outside the US or for our product candidates in the US, Europe, Japan or other markets;•failure of third parties on which we are dependent to manufacture sufficient quantities of ARIKAYCE or our product candidates for commercial orclinical needs, to conduct our clinical trials, or to comply with our agreements or laws and regulations that impact our business;•our inability to attract and retain key personnel or to effectively manage our growth;•our inability to adapt to our highly competitive and changing environment;•our inability to adequately protect our intellectual property rights or prevent disclosure of our trade secrets and other proprietary information andcosts associated with litigation or other proceedings related to such matters;4Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contents•restrictions or other obligations imposed on us by agreements related to ARIKAYCE or our product candidates, including our license agreementswith PARI and AstraZeneca AB (AstraZeneca), and failure to comply with our obligations under such agreements;•the cost and potential reputational damage resulting from litigation to which we are or may become a party, including product liability claims;•limited experience operating internationally;•changes in laws and regulations applicable to our business and failure to comply with such laws and regulations; and•inability to repay our existing indebtedness and uncertainties with respect to our ability to access future capital.We caution readers not to place undue reliance on any such forward-looking statements, which speak only as of the date they are made. Any forward-looking statement is based on information current as of the date of this Annual Report on 10-K and speaks only as of the date on which such statement ismade. Actual events or results may differ materially from the results, plans, intentions or expectations anticipated in these forward-looking statements as aresult of a variety of factors, many of which are beyond our control. More information on factors that could cause actual results to differ materially fromthose anticipated is included from time to time in our reports filed with the Securities and Exchange Commission (SEC), including, but not limited to, thosedescribed in the sections titled “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations” included inthis Annual Report on Form 10-K. We disclaim any obligation, except as specifically required by law and the rules of the SEC, to publicly update or reviseany such statements to reflect any change in our expectations or in events, conditions or circumstances on which any such statements may be based, or thatmay affect the likelihood that actual results will differ from those set forth in the forward-looking statements..5Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsPART IITEM 1. BUSINESSBusiness OverviewWe are a global biopharmaceutical company on a mission to transform the lives of patients with serious and rare diseases. Our first commercialproduct, ARIKAYCE (amikacin liposome inhalation suspension), received accelerated approval in the United States (US) on September 28, 2018 for thetreatment of Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen for adult patients with limited or noalternative treatment options in a refractory setting, as defined by patients who do not achieve negative sputum cultures after a minimum of 6 consecutivemonths of a multidrug background regimen therapy. MAC lung disease is a rare and often chronic infection that can cause irreversible lung damage and canbe fatal. Our clinical-stage pipeline includes INS1007 and INS1009. INS1007 is a novel oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP1) withtherapeutic potential in non-cystic fibrosis (non-CF) bronchiectasis and other inflammatory diseases. INS1009 is an inhaled formulation of a treprostinilprodrug that may offer a differentiated product profile for rare pulmonary disorders, including pulmonary arterial hypertension (PAH).The table below summarizes the current status and anticipated milestones for ARIKAYCE and our product candidates INS1007 and INS1009.PrincipalProduct/Product Candidate StatusNext Expected MilestonesARIKAYCE for MAClung disease• We continue to focus on having a successful commercial launchof ARIKAYCE in the US for appropriate patients. We begancommercial shipments of ARIKAYCE in October 2018.• In September 2018, the FDA granted accelerated approval ofARIKAYCE for the treatment of refractory MAC lung diseaseas part of a combination antibacterial drug regimen for adultpatients who have limited or no alternative treatment options.• The FDA has designated ARIKAYCE as an orphan drug and aqualified infectious disease product (QIDP) for nontuberculousmycobacterial (NTM) lung disease, and the EuropeanCommission has granted an orphan designation for ARIKAYCEfor the treatment of NTM lung disease. • We intend to submit regulatory filings for ARIKAYCE in Europein mid-2019 and Japan in the first half of 2020. If approved, weexpect ARIKAYCE would be the first inhaled therapy specificallyindicated for the treatment of MAC lung disease in Europe andJapan.• If approved, we plan to commercialize ARIKAYCE in certaincountries in Europe, Japan and certain other countries.• We intend to collaborate with the FDA on, and invest in, the post-approval confirmatory clinical trial required by the FDA to supportfull approval and intend to complete the design and protocol of theconfirmatory study during the first half of 2019. We also intend tocollaborate with the FDA on lifecycle management programs.INS1007 (oral reversible inhibitorof DPP1) for non-CF bronchiectasis and other rarediseases• We are enrolling patients in the WILLOW study, a global phase2, randomized, double-blind, placebo-controlled, parallel-group,multi-center clinical study to assess the efficacy, safety andtolerability, and pharmacokinetics of INS1007 administered oncedaily for 24 weeks in subjects with non-CF bronchiectasis.• We expect to complete enrollment in the WILLOW clinical study ofINS1007 in mid-2019.• We are exploring the potential of INS1007 in various neutrophil-driven inflammatory conditions.INS1009 (inhaled formulation of atreprostinil prodrug) for rarepulmonary disorders• The results of our phase 1 study of INS1009 were presented atthe European Respiratory Society international congress inSeptember 2016.• We believe INS1009 may offer a differentiated product profile forrare pulmonary disorders, including PAH, and we are currentlyevaluating our options to advance its development includingexploring its use as an inhaled dry powder formulation.Our earlier-stage pipeline includes preclinical compounds that we are evaluating in multiple rare diseases of unmet medical need, including grampositive pulmonary infections in CF, NTM lung disease and refractory localized infections involving biofilm. To complement our internal research anddevelopment, we actively evaluate in-licensing and acquisition opportunities for a broad range of rare diseases.Our Strategy6Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contents Our strategy focuses on the needs of patients with rare diseases. We secured US regulatory approval of ARIKAYCE for the treatment of refractoryMAC lung disease in patients with limited or no alternative treatment options. We are currently primarily focused on the US commercial launch ofARIKAYCE. We are not aware of any other approved inhaled therapies specifically indicated to treat MAC lung disease in North America, Europe or Japan.We believe that ARIKAYCE has the potential to prove beneficial in other patients with MAC, as well as in other infections. We are also advancing earlier-stage programs in other rare pulmonary disorders. Our current priorities are as follows: •Continue our efforts to ensure a successful US launch of ARIKAYCE;•Complete the design and protocol of the confirmatory clinical trial during the first half of 2019 required for the full US approval of ARIKAYCEby the FDA in patients with MAC;•Accelerate our global expansion efforts to support potential regulatory filings for ARIKAYCE in Europe in mid-2019 and Japan in the first halfof 2020;•Advance our pipeline, which is intended to bring additional therapies to market for patients with serious and rare diseases, includingcompleting enrollment in the WILLOW study, our six-month Phase 2 trial of INS1007 in patients with non-cystic fibrosis bronchiectasis, inmid-2019.•Ensure our product supply chain will support the global commercialization and potential future lifecycle management programs of ARIKAYCE;•Develop the core value dossier to support the reimbursement for ARIKAYCE in the US, Europe and Japan;•Obtain determinations of coverage and reimbursement in the US for ARIKAYCE from governmental and other third-party payors;•Support further research and lifecycle management strategies for ARIKAYCE in the US, including exploring the potential use of ARIKAYCE aspart of a front-line, multi-drug regimen and as a maintenance therapy to prevent recurrence (defined as true relapse or reinfection) of MAC lungdisease;•Explore INS1009 for use as an inhaled dry powder formulation and generating preclinical findings from our earlier-stage programs; and•Expand our rare disease pipeline through corporate development.ARIKAYCE for Patients with MAC Lung Disease ARIKAYCE is our first approved product. ARIKAYCE received accelerated approval in the US on September 28, 2018 for the treatment of refractoryMAC lung disease as part of a combination antibacterial drug regimen for adult patients with limited or no alternative treatment options. MAC lung diseaseis a rare and often chronic infection that can cause irreversible lung damage and can be fatal. Amikacin solution for parenteral administration is anestablished drug that has activity against a variety of NTM; however, its use is limited by the need to administer it intravenously and by toxicity to hearing,balance, and kidney function (Peloquin et al., 2004). Unlike amikacin solution for intravenous administration, our proprietary Pulmovance™ technologyuses charge-neutral liposomes to deliver amikacin directly to the lungs where liposomal amikacin is taken up by the lung macrophages where the MACinfection resides. This technology also prolongs the release of amikacin in the lungs, while minimizing systemic exposure, thereby offering the potential fordecreased systemic toxicities. ARIKAYCE's ability to deliver high levels of amikacin directly to the lung and sites of MAC infection via the use of ourPulmovance technology, distinguishes it from intravenous amikacin. ARIKAYCE is administered once-daily, using Lamira®, an inhalation devicedeveloped and manufactured by PARI. Lamira is a portable nebulizer that enables aerosolization of liquid medications via a vibrating, perforated membrane,and was designed specifically for ARIKAYCE delivery. The FDA has designated ARIKAYCE as an orphan drug and a QIDP for NTM lung disease. Orphan designated drugs are eligible for seven years ofexclusivity for the orphan indication. QIDP designation features an additional five years of exclusivity for the designated indication. The FDA granted a totalof 12 years of exclusivity in the indication for which ARIKAYCE was approved.US Marketing Approval7Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsIn March 2018, we submitted a new drug application (NDA) for ARIKAYCE to the FDA pursuant to Section 506(c) of the Federal Food Drug andCosmetic Act and 21 C.F.R. Part 314 Subpart H (Accelerated Approval of New Drugs for Serious or Life-Threatening Illnesses) (Subpart H). Acceleratedapproval allows drugs that (i) are being developed to treat a serious or life-threatening disease or condition and (ii) provide a meaningful therapeutic benefitover existing treatments to be approved substantially based on an intermediate endpoint or a surrogate endpoint that is reasonably likely to predict clinicalbenefit, rather than a clinical endpoint such as survival or irreversible morbidity. The FDA granted our request for a priority review and set a PrescriptionDrug Use Fee Act (PDUFA) action date of September 28, 2018. On August 7, 2018, the FDA Antimicrobial Drugs Advisory Committee voted in favor of thesafety and effectiveness of ARIKAYCE as part of a combination antibacterial drug regimen for adults with MAC lung disease who have limited or notreatment options. The committee also voted in favor of the surrogate endpoint of sputum culture conversion used in the Phase 3 CONVERT study beingreasonably likely to predict clinical benefit. In a separate vote, the committee voted that there was insufficient existing evidence of the safety andeffectiveness of ARIKAYCE in the broader population of adult patients with MAC lung disease. On September 28, 2018, the FDA granted approval forARIKAYCE under the Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD) for the treatment of refractory MAC lung disease as part ofa combination antibacterial drug regimen for adult patients with limited or no alternative treatment options via the accelerated approval pathway. LPAD,which was enacted as part of the 21st Century Cures Act, serves to advance the development of new antibacterial drugs to treat serious or life-threateninginfections in limited populations of patients with unmet needs. As required for drugs approved under the LPAD pathway, labeling for ARIKAYCE includescertain statements to convey that the drug has been shown to be safe and effective only for use in a limited population.As a condition of accelerated approval, we must conduct a post-approval confirmatory clinical trial. The required confirmatory trial, which iscurrently under discussion with FDA, is proposed to be a randomized, double-blind, placebo-controlled clinical trial to assess and describe the clinicalbenefit of ARIKAYCE in patients with MAC lung disease. The trial will evaluate the effect of ARIKAYCE on a clinically meaningful endpoint, as comparedto an appropriate control, in the intended patient population of patients with MAC lung disease. Pursuant to the timetable agreed upon with the FDA, thestudy protocol is expected to be finalized during the first half of 2019, with trial results to be reported by 2024. Continued approval of ARIKAYCE will becontingent upon verification and description of clinical benefit in this study.Clinical TrialsAccelerated approval of ARIKAYCE was supported by preliminary data from our CONVERT study, a global Phase 3 study evaluating the safety andefficacy of ARIKAYCE in adult patients with refractory MAC lung disease, using achievement of sputum culture conversion (defined as three consecutivenegative monthly sputum cultures) by Month 6 as the primary endpoint. Patients who achieved sputum culture conversion by Month 6 continued in theCONVERT study for an additional 12 months of treatment following the first monthly negative sputum culture in order to assess the durability of cultureconversion, as defined by patients that have completed treatment and continued in the CONVERT study off all therapy for three months. We previouslyreported interim durability data as of December 2017, in which 60.9% of patients (28/46) who had achieved the primary endpoint at Month 6 on ARIKAYCEplus guidelines-based therapy (GBT) remained culture negative three months off all therapy, compared to 0.0% of patients (0/7) who had achieved theprimary endpoint at Month 6 on GBT only. Final durability data for patients three months off all therapy were consistent with these interim data, and safetydata for these patients were consistent with safety data previously reported for patients by Month 6 of the CONVERT study. The CONVERT study isongoing. Patients who did not culture convert by Month 6 may have been eligible to enroll in our 312 study, an open-label extension study for these non-converting patients who completed six months of treatment in the CONVERT study. The primary objective of the 312 study was to evaluate the long-termsafety and tolerability of ARIKAYCE in combination with a standard multi-drug regimen. The secondary objectives of the 312 study included evaluating theproportion of subjects achieving culture conversion (defined in the same way as the CONVERT study) by Month 6 and the proportion of subjects achievingculture conversion by Month 12, which was the end of treatment. We previously reported interim data as of December 2017 for patients in the 312 study, with28.4% of patients who received GBT only in the CONVERT study (19/67) and 12.3% of patients who had received ARIKAYCE plus GBT in the CONVERTstudy (7/57) achieving culture conversion by Month 6 of the 312 study. The 312 study has concluded. Final efficacy data regarding culture conversion wereconsistent with these interim data. We are continuing to analyze the safety and efficacy data from the 312 study, but we have not identified any new safetysignals.Further Research and Lifecycle Management We are currently exploring and supporting research and lifecycle management programs for ARIKAYCE in the US beyond treatment of refractoryMAC lung disease as part of a combination antibacterial regimen for adult patients who have limited or no treatment options. Specifically, we are evaluatingfuture study designs focusing on the MAC lung disease8Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentstreatment pathway, including front-line treatment and maintenance to prevent recurrence (defined as true relapse or reinfection) of MAC lung disease. Asnoted above, we plan to conduct our required confirmatory trial to assess and describe the clinical benefit of ARIKAYCE in patients with MAC lung disease.If the data from the CONVERT study are sufficient to support our marketing authorization applications (MAAs) in Europe and Japan and thoseregulatory bodies approve ARIKAYCE, lifecycle management studies could potentially enable us to reach more patients worldwide. In addition, the use ofARIKAYCE to treat infections caused by non-MAC NTM species, such as M. abscessus, is being evaluated. These initiatives include investigator-initiatedstudies, which are clinical studies initiated and sponsored by physicians or research institutions with funding from us, and may also include new clinicalstudies sponsored by us. Market Opportunity for ARIKAYCE in MAC Lung DiseaseNTM lung disease is associated with increased rates of morbidity and mortality, and MAC is the predominant pathogenic species in NTM lungdisease in the US, Europe and Japan. The prevalence of NTM lung disease has increased over the past two decades, and we believe it is an emerging publichealth concern worldwide. Based on an analysis conducted in 2017 using information from external sources, including market research funded by us andthird parties, and internal analyses and calculations, we estimated potential patient populations for 2018 in the US, the EU5 (comprised of France, Germany,Italy, Spain and the United Kingdom) and Japan as follows:Potential Market Estimated Number of Patientswith Diagnosed NTM LungDiseaseEstimated Number of PatientsTreated for MAC Lung DiseaseEstimated Number of MAC lungdisease Patients Refractory toTreatment**United States 75,000-105,00040,000-50,00010,000-15,000EU5 14,0004,4001,400Japan 125,000-145,00060,000-70,00015,000-18,000** ARIKAYCE received accelerated approval for this population in the US in September 2018.We are not aware of any other approved inhaled therapies specifically indicated for NTM lung disease in North America, Europe or Japan. Currentguideline-based approaches for NTM lung disease, including those from the American Thoracic Society and Infectious Diseases Society of America, involvemulti-drug regimens not approved for the treatment of NTM lung disease and treatment that could last two years or more. Based on a burden of illness studythat we conducted in the US with a major medical benefits provider, we previously concluded that patients with NTM lung disease are costly to healthcareplans, while a recent claims-based study in the US has shown that patients with NTM lung disease have higher resource utilization and costs than their ageand gender-matched controls. Accordingly, we believe that a significant market opportunity for ARIKAYCE in NTM lung disease exists in the US andinternationally. We are currently exploring the MAC lung disease market opportunity for ARIKAYCE in Japan and Europe. The CONVERT study included acomprehensive pharmacokinetic sub-study in Japanese subjects in lieu of a separate local pharmacokinetic study in Japan, as agreed with thePharmaceuticals and Medical Devices Agency (PMDA). If the data from the CONVERT study are sufficient to support our MAAs, we expect to submitregulatory filings in Europe in mid-2019 and Japan in the first half of 2020. We established a Japanese subsidiary and, in 2018, began hiring localemployees, including a general manager, to manage our regulatory and pre-commercial activities.Product Pipeline INS1007 INS1007 is a small molecule, oral, reversible inhibitor of DPP1, which we licensed from AstraZeneca in October 2016. DPP1 is an enzymeresponsible for activating neutrophil serine proteases in neutrophils when they are formed in the bone marrow. Neutrophils are the most common type ofwhite blood cell and play an essential role in pathogen destruction and inflammatory mediation. Neutrophils contain the neutrophil serine proteases(including neutrophil elastase, proteinase 3, and cathepsin G) that have been implicated in a variety of inflammatory diseases. In chronic inflammatory lungdiseases, neutrophils accumulate in the airways and release active neutrophil serine proteases in excess that cause lung destruction and inflammation.INS1007 may decrease the damaging effects of inflammatory diseases, such as non-CF bronchiectasis, by inhibiting DPP1 and its activation of neutrophilserine proteases. Non-CF bronchiectasis is a progressive pulmonary disorder in which the bronchi become permanently dilated due to chronic inflammationand infection. Currently, there is no cure, and we are not aware of any FDA-approved therapies specifically indicated for non-CF bronchiectasis.9Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contents The WILLOW Study The WILLOW study is a global phase 2, randomized, double-blind, placebo-controlled, parallel group, multi-center clinical study to assess theefficacy, safety and tolerability, and pharmacokinetics of INS1007 administered once daily for 24 weeks in subjects with non-CF bronchiectasis. Wecommenced enrollment in the WILLOW study in December 2017, which we expect to complete in mid-2019. In addition, we are exploring the potential ofINS1007 in various neutrophil-driven inflammatory conditions. INS1009 INS1009 is an investigational inhaled treprostinil prodrug formulation that has the potential to address certain of the current limitations of existingprostanoid therapies. We believe that INS1009 prolongs duration of effect and may provide PAH patients with greater consistency in pulmonary arterialpressure reduction over time. Current inhaled prostanoid therapies must be dosed four to nine times per day for the treatment of PAH. Reducing dosefrequency has the potential to ease patient burden and improve compliance. Additionally, we believe that INS1009 may be associated with fewer side effects,including elevated heart rate, low blood pressure, and severity and/or frequency of cough, associated with high initial drug levels and local upper airwayexposure when using current inhaled prostanoid therapies. We believe INS1009 may offer a differentiated product profile for rare pulmonary disorders,including PAH, and we are currently evaluating our options to advance its development, including exploring its use as an inhaled dry powder formulation. Corporate DevelopmentIn October 2016, we exclusively licensed global rights to INS1007 from AstraZeneca and we plan to continue to develop, acquire, in license or co-promote other products and product candidates that address rare diseases. We are focused broadly on rare disease therapeutics and prioritizing those areas thatbest align with our core competencies.ManufacturingWe do not have any in-house manufacturing capability other than for small-scale pre-clinical development programs, and depend completely on asmall number of third-party manufacturers and suppliers for the manufacture of our product candidates for use in clinical trials. We plan to rely on third-partymanufacturers and suppliers for the commercial manufacture and supply of any product candidates that we commercialize. ARIKAYCE is manufacturedcurrently by Therapure Biopharma Inc. (Therapure) in Canada at a 200 kilogram (kg) scale and by Ajinimoto Althea, Inc. (Althea) in the US at a 50 kg scale.For additional information about our agreements with Therapure and Althea, see License and Other Agreements—ARIKAYCE-Related Agreements.In October 2017, we entered into certain agreements with Patheon UK Limited (Patheon) related to increasing our long-term production capacity forARIKAYCE commercial inventory. The agreements provide for Patheon to manufacture and supply ARIKAYCE for our long-term anticipated commercialneeds. Under these agreements, we are required to deliver to Patheon the required raw materials, including active pharmaceutical ingredients, and certainfixed assets needed to manufacture ARIKAYCE. The investment in the long-term production capacity build-out, including these agreements, and relatedagreements or purchase orders with third parties for raw materials and fixed assets, is estimated to be approximately $60 million. In addition, we have acommercialization agreement with PARI, the manufacturer of our drug delivery nebulizer for ARIKAYCE, to address our commercial supply needs(Commercialization Agreement).In May 2017, we entered into a commercial supply agreement with AstraZeneca related to certain short-term production needs for INS1007. Weexpect our future requirements for INS1007, beyond phase 2, will be manufactured by a contract manufacturing organization (CMO).We currently produce INS1009 and plan to utilize third parties to manufacture INS1009 at a larger scale and to manufacture the delivery device.Intellectual PropertyWe own or license rights to more than 350 issued patents and pending patent applications in the US and in foreign countries, including more than175 issued patents and pending patent applications related to ARIKAYCE. Our success depends in large part on our ability to maintain proprietary protectionsurrounding our product candidates, technology and know-how; to operate without infringing the proprietary rights of others; and to prevent others frominfringing our proprietary rights. We actively seek patent protection by filing patent applications, including on inventions that are important to thedevelopment of our business in the US, Europe, Japan, Canada, and selected other foreign markets that we consider key for our product candidates. Theseinternational markets generally include Australia, China, India, Israel, and Mexico.10Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsOur patent strategy includes obtaining patent protection, where possible, on compositions of matter, methods of manufacture, methods of use,methods of treatment, dosing and administration regimens and formulations. We also rely on trade secrets, know-how, continuing technological innovation,in-licensing and partnership opportunities to develop and maintain our proprietary position.We monitor for activities that may infringe our proprietary rights, as well as the progression of third-party patent applications that may have thepotential to create blocks to our products or otherwise interfere with the development of our business. We are aware, for example, of US patents, andcorresponding international counterparts, owned by third parties that contain claims related to treating lung infections using inhaled antibiotics. If any ofthese patents were to be asserted against us, we do not believe that our proposed products would be found to infringe any valid claim of these patents.Reflecting our commitment to safeguarding proprietary information, we require our employees, consultants, advisors, collaborators and other third-party partners to sign confidentiality agreements to protect the exchange of proprietary materials and information. We also seek to preserve the integrity andconfidentiality of our data and trade secrets by maintaining physical security of our premises and physical and electronic security of our informationtechnology systems.ARIKAYCE Patents and Trade SecretsOf the patents and applications related to ARIKAYCE, there are nine issued US patents that cover the ARIKAYCE composition and its use intreating NTM. These patents are listed in the FDA Orange Book. These patents and their expiration dates are as follows:•US Patent No. 7,718,189 (expires June 6, 2025)•US Patent No. 8,226,975 (expires August 15, 2028)•US Patent No. 8,632,804 (expires December 5, 2026)•US Patent No. 8,802,137 (expires April 8, 2024)•US Patent No. 8,679,532 (expires December 5, 2026)•US Patent No. 8,642,075 (expires December 5, 2026)•US Patent No. 9,566,234 (expires January 18, 2034)•US Patent No. 9,827,317 (expires April 8, 2024)•US Patent No. 9,895,385 (expires May 15, 2035)In addition, we own six pending US patent applications that cover the ARIKAYCE composition and/or its use in treating NTM. We also own apending US application that covers methods for making ARIKAYCE. These patent applications, if issued as patents in their current form, may be eligible forlisting in the FDA Orange Book for ARIKAYCE.Four patents have been granted by the European Patent Office (EPO) (European Patent Nos. 1581236, 1909759, 1962805 and 2363114) that relateto ARIKAYCE and its use in treating NTM. In addition, we have five applications pending before the EPO that relate to ARIKAYCE and its use in treatingNTM lung disease. We also have a pending European application that describes certain methods of making ARIKAYCE. More than 40 patents have alsobeen issued in other major foreign markets, e.g., Japan, China, Korea, Australia, and India, that relate to ARIKAYCE and/or methods of using ARIKAYCE fortreating various pulmonary disorders, including NTM lung disease. More than 60 foreign patent applications are pending that relate to the ARIKAYCEcomposition and/or its use in treating various pulmonary disorders, including NTM lung disease. We anticipate that in the US, we will have potential patentcoverage for ARIKAYCE and its use in treating NTM lung disease, through May 15, 2035.European Patent No. 2363114 was opposed by Generics (UK) Ltd, a wholly-owned subsidiary of Mylan NV, and was revoked in November 2017.We have appealed that decision, and the patent remains enforceable during the appeal. European Patent No. 1909759 (the '759 patent), owned by us, waspreviously opposed by Generics (UK) Ltd. A hearing was held on October 19, 2015, during which we submitted amended claims. The European Patent OfficeOpposition Division (EPOOD) maintained the patent as amended and Generics (UK) Ltd appealed the decision. The EPO Technical Board of Appeals heardarguments related to the appeal on January 8, 2019 and the product claims of the patent were held invalid. The method of manufacture claims was remitted tothe EPOOD for further consideration, and remain enforceable. We have a divisional application pending that claims priority from the ‘759 patent where weare pursuing product claims of varying scope. European Patent No. 1962805, which expires approximately five months after the ‘759 patent (December 5,2026 vs. July 19, 2026), also includes claims related to ARIKAYCE and its use in treating NTM lung disease. All of our issued European patents haveexpiration dates that would fall within the regulatory exclusivity period for ARIKAYCE, should ARIKAYCE ultimately gain approval by the EMA.Through our agreements with PARI, we have license rights to US and foreign patents and applications that cover the Lamira Nebulizer Systemmedical device through January 18, 2034. We have entered into a commercial supply agreement with PARI and we also have rights to use the nebulizers inexpanded access programs and clinical trials.11Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsThe basic terms of utility patents issued in the US are the longer of 17 years from the issue date or 20 years from the earliest effective filing date, ifthe patent was in force on or was issued from a patent application that was filed prior to June 8, 1995; or 20 years from the earliest effective filing date, if thepatent application was filed on or after June 8, 1995. All ARIKAYCE patent applications have earliest effective filing dates falling after June 8, 1995. Thebasic term of foreign utility patents may vary in accordance with provisions of applicable local law, but is typically 20 years from the earliest effective filingdate.INS1007 PatentsThrough our agreement with AstraZeneca, we have licensed US Patent Nos. 9,522,894 and 9,815,805, which have claims directed to INS1007 andmethods for using INS1007. Each expires January 21, 2035 (not taking into account any potential patent term extension). Counterpart patent applications arepending throughout the world and a continuation application is pending in the US.INS1009 PatentsWe own US Patent No. 9,255,064 (expires October 24, 2034), which is the first patent to issue with claims covering hexadecyl-treprostinil, thetreprostinil component of INS1009. Other treprostinil prodrugs are also claimed and described in the patent. We also own US Patent No. 9,469,600, which hasclaims directed to INS1009 and other treprostinil prodrug formulations and expires October 24, 2034. We also own US Patent No. 10,010,518, which hasclaims directed to methods of treating pulmonary hypertension, including PAH, with INS1009 and other treprostinil prodrug formulations and expiresOctober 24, 2034. Counterpart patent applications to these US Patents are pending in Europe, Japan and other foreign jurisdictions.We own pending patent applications that relate to methods for using treprostinil prodrugs and formulations comprising the same, includingINS1009 in treating patients with PAH and other diseases, as well as methods for manufacturing such treprostinil prodrugs and formulations.TrademarksIn addition to our patents and trade secrets, we have filed applications to register certain trademarks in the US and/or abroad, including INSMEDand ARIKAYCE. At present, we have received a registration for the INSMED and ARIKAYCE marks from the US Patent and Trademark Office (USPTO). Wehave also received foreign notices of allowance or registrations for the INSMED and ARIKAYCE marks, among others. The European Medicines Agency(EMA) has indicated it has no objection to our use of the name ARIKAYCE, and the FDA has approved our use of the name ARIKAYCE as the trade name foramikacin liposome inhalation suspension. Our ability to obtain and maintain trademark registrations will in certain geographical locations depend onmaking use of the mark in commerce on or in connection with our products and approval of the trademarks for our products by regulatory authorities in eachcountry.License and Other AgreementsARIKAYCE-related AgreementsWe currently rely, and will continue to rely, on agreements with a number of third parties in connection with the development and manufacture ofARIKAYCE.PARI Pharma GmbHWe have a licensing agreement with PARI for use of the optimized Lamira Nebulizer System for delivery of ARIKAYCE in treating patients withNTM lung infections, cystic fibrosis (CF) and bronchiectasis. Under the licensing agreement, we have rights under several US and foreign issued patents, andpatent applications involving improvements to the optimized Lamira Nebulizer System, to exploit such system with ARIKAYCE for the treatment of suchindications, but we cannot manufacture such nebulizers except as permitted under our Commercialization Agreement with PARI. We currently have rights touse the nebulizers in expanded access programs and clinical trials. The Lamira Nebulizer System is labeled as investigational for use in our clinical trials inJapan, Canada and Australia and must receive regulatory approval before we can market ARIKAYCE; the Lamira Nebulizer System has been approved for usein the US (in combination with ARIKAYCE) and EU.We have certain obligations under this licensing agreement in relation to specified licensed indications. With respect to CF, we are obligated touse commercially reasonable efforts to develop, obtain regulatory and reimbursement approval, market and sell ARIKAYCE in two or more major Europeancountries. With respect to NTM and bronchiectasis, we have specific obligations to use commercially reasonable efforts to achieve certain developmental andregulatory milestones by set deadlines. Additionally, for NTM, we are obligated to use commercially reasonable efforts to achieve certain commercialmilestones in the US and Europe. The consequences of our failing to use commercially reasonable efforts to achieve these milestones are context-specific, butinclude ending PARI's non-compete obligation, making the license non-exclusive and12Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentsterminating the license, in each case with respect to the applicable indication. Termination of the licensing agreement or loss of exclusive rights may occur ifwe fail to meet our obligations, including payment of royalties to PARI, or if we do not meet certain milestones contained in the licensing agreement such asobtaining marketing approval in an EU country.Under the licensing agreement, we paid PARI an upfront license fee and milestone payments. Upon FDA acceptance of our NDA and thesubsequent FDA approval of ARIKAYCE, we paid PARI additional milestone payments of €1.0 million and €1.5 million, respectively. In addition, PARI isentitled to receive future milestone payments up to €0.5 million in cash based on achievement of first receipt of marketing approval in a major EU country forARIKAYCE and the device. In October 2017, we exercised an option to buy-down the royalties payable to PARI. PARI is now entitled to receive royaltypayments in the mid-single digits on the annual global net sales of ARIKAYCE pursuant to the licensing agreement, subject to certain specified annualminimum royalties.This licensing agreement will remain in effect on a country-by-country basis until the final royalty payments have been made with respect to thelast country in which ARIKAYCE is sold, or until the agreement is otherwise terminated by either party. We have the right to terminate this licensingagreement upon written notice for PARI's uncured material breach, if PARI is the subject of specified bankruptcy or liquidation events, or if PARI fails toreach certain specified obligations. PARI has the right to terminate this licensing agreement upon written notice for our uncured material breach, if we are thesubject of specified bankruptcy or liquidation events, if we assign or otherwise transfer the agreement to a third-party that does not agree to assume all of ourrights and obligations set forth in the agreement, or if we fail to reach certain specified milestones.In July 2014, we entered into a Commercialization Agreement with PARI for the manufacture and supply of Lamira nebulizer systems and relatedaccessories (the Device) as optimized for use with ARIKAYCE. Under the Commercialization Agreement, PARI manufactures the Device except in the case ofcertain defined supply failures, when we will have the right to make the Device and have it made by third parties (but not certain third parties deemed underthe Commercialization Agreement to compete with PARI). The Commercialization Agreement has an initial term of 15 years that began to run in October2018 (the Initial Term). The term of the Commercialization Agreement may be extended by us for an additional five years by providing written notice toPARI at least one year prior to the expiration of the Initial Term.AltheaIn September 2015, we entered into a Commercial Fill/Finish Services Agreement (the Fill/Finish Agreement) with Althea to produce, on a non-exclusive basis, ARIKAYCE in finished dosage form at a 50 kg scale. We are obligated to pay a minimum of $2.7 million for the batches of ARIKAYCEproduced by Althea each calendar year during the term of the Fill/Finish Agreement. The Fill/Finish Agreement became effective as of January 1, 2015, and,following an extension in 2018, will remain in effect through December 31, 2021. The Fill/Finish Agreement may be extended for additional two-yearperiods upon mutual written agreement of the Company and Althea at least one year prior to the expiration of its then-current term. We have expensed at leastthe required minimum in each year of the contract.Either we or Althea may terminate the Fill/Finish Agreement upon the occurrence of certain events, including (i) material breach of the Fill/FinishAgreement by either party, provided such breach is not cured within 30 days after receipt by the breaching party of written notice of the breach or(ii) insolvency or bankruptcy of the other party. In addition, we may terminate the Fill/Finish Agreement without cause with 12 months' prior written noticeto Althea, and Althea may terminate the Agreement without cause with 24 months' prior written notice to us.TherapureIn February 2014, we entered into a contract manufacturing agreement with Therapure for the manufacture of ARIKAYCE, on a non-exclusivebasis, at a 200 kg scale. Pursuant to the agreement, we collaborated with Therapure to construct a production area for the manufacture of ARIKAYCE inTherapure's existing manufacturing facility in Mississauga, Ontario, Canada. The agreement has an initial term of five years, which began in October 2018,and will renew automatically for successive periods of two years each, unless terminated by either party by providing the required two years' prior writtennotice to the other party. Notwithstanding the foregoing, the parties have rights and obligations under the agreement prior to the commencement of the initialterm. Under the agreement, we are obligated to pay certain minimum amounts for the batches of ARIKAYCE produced each calendar year. The agreementallows for termination by either party upon the occurrence of certain events, including (i) the material breach by the other party of any provision of theagreement or the quality agreement expected to be entered into between the parties, and (ii) the default or bankruptcy of the other party. In addition, we mayterminate the agreement for any reason upon no fewer than 180 days' advance notice.Patheon and related agreementsIn October 2017, we entered into certain agreements with Patheon related to the increase of our long-term production capacity for ARIKAYCE. Theagreements provide for Patheon to manufacture and supply ARIKAYCE for our anticipated commercial needs. Under these agreements, we are required todeliver to Patheon the required raw materials, including active pharmaceutical ingredients, and certain fixed assets needed to manufactureARIKAYCE. Patheon's supply obligations will13Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentscommence once certain technology transfer and construction services are completed. Our manufacturing and supply agreement with Patheon will remain ineffect for a fixed initial term, after which it will continue for successive renewal terms unless either we or Patheon have given written notice of termination.The technology transfer agreement will expire when the parties agree that the technology transfer services have been completed. The agreements may also beterminated under certain other circumstances, including by either party due to a material uncured breach of the other party or the other party’s insolvency.These early termination clauses may reduce the amounts due to the relevant parties. The investment in our long-term production capacity build-out,including under the Patheon agreements and related agreements or purchase orders with third parties for raw materials and fixed assets, is estimated to beapproximately $60 million.SynteractHCR, Inc. (Synteract)We entered into a services agreement with Synteract pursuant to which we retained Synteract to perform implementation and management servicesin connection with the CONVERT study. We may terminate the services agreement or any work order for any reason and without cause with 30 days' writtennotice. Either party may terminate the agreement in the event of a material breach or bankruptcy petition by the other party or, if any approval from aregulatory authority is revoked, suspended or expires without renewal. We anticipate that aggregate costs relating to all work orders for the CONVERT studywill be approximately $48 million over the period of the study. In April 2015, we entered into a work order with Synteract to perform implementation andmanagement services for the 312 study.Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT)In 2004 and 2009, we entered into research funding agreements with CFFT whereby we received $1.7 million and $2.2 million for each respectiveagreement in research funding for the development of ARIKAYCE. If ARIKAYCE becomes an approved product for certain infections in CF patients or suchinfections in human pulmonary disease in the US, we will owe a payment to CFFT of up to $13.4 million that is payable over a three-year period afterregulatory approval in the US. Furthermore, if certain global sales milestones are met within five years of the drug commercialization, we would oweadditional payments of $3.9 million. Under the 2009 agreement, in the event we terminate development of ARIKAYCE for CF prior to first commercial saleof a product containing ARIKAYCE for a period of 360 continuous days, and such termination is not for reasons outside of our reasonable control, then atCFFT's election and within 180 days of such termination, CFFT (1) may elect to develop ARIKAYCE for CF and (2) will have the right to receive from us anexclusive (subject to certain exceptions), royalty-free, sub-licensable license to use, develop, sell and commercialize a product containing ARIKAYCE in thetreatment of certain infections in CF patients or pulmonary disease associated with CF.INS1007-related AgreementsSyneos HealthWe entered into a services agreement with Syneos Health (Syneos) pursuant to which we retained Syneos to perform implementation andmanagement services in connection with the WILLOW study. We may terminate the services agreement or any work order for any reason and without causewith 30 days' written notice. Either party may terminate the agreement in the event of a material breach or bankruptcy petition by the other party or, if anyapproval from a regulatory authority is revoked, suspended or expires without renewal. We anticipate that aggregate costs relating to all work orders for theWILLOW study will be approximately $21 million over the period of the study.AstraZenecaIn October 2016, we entered into the AZ License Agreement, pursuant to which AstraZeneca granted us exclusive global rights for the purpose ofdeveloping and commercializing AZD7986 (renamed INS1007). In consideration of the licenses and other rights granted by AstraZeneca, we made an upfrontpayment of $30.0 million in late October 2016. We are obligated to make a series of contingent milestone payments to AstraZeneca totaling up to anadditional $85.0 million upon the achievement of clinical development and regulatory filing milestones. If we elect to develop INS1007 for a secondindication, we will be obligated to make an additional series of contingent milestone payments totaling up to $42.5 million. We are not obligated to makeany additional milestone payments for additional indications. In addition, we have agreed to pay AstraZeneca tiered royalties ranging from a high single-digit to mid-teens on net sales of any approved product based on INS1007 and one additional payment of $35.0 million upon the first achievement of$1 billion in annual net sales. The AZ License Agreement provides AstraZeneca with the option to negotiate a future agreement with us forcommercialization of INS1007 in chronic obstructive pulmonary disease or asthma. If we fail to comply with our obligations under our agreements withAstraZeneca (including, among other things, if we fail to use commercially reasonable efforts to develop and commercialize a product based on INS1007, orwe are subject to a bankruptcy or insolvency), AstraZeneca would have the right to terminate the license.CompetitionThe biotechnology and pharmaceutical industries are highly competitive. We face potential competitors from many different areas includingcommercial pharmaceutical, biotechnology and device companies, academic institutions and14Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentsscientists, other smaller or earlier stage companies and non-profit organizations developing anti-infective drugs and drugs for respiratory diseases. Many ofthese companies have greater human and financial resources and may have product candidates in more advanced stages of development and may reach themarket before our product candidates. Competitors may develop products that are more effective, safer or less expensive or that have better tolerability orconvenience. We also may face generic competitors where third-party payors will encourage use of the generic products. Although we believe that ourformulation delivery technology, respiratory and anti-infective expertise, experience and knowledge in our specific areas of focus provide us withcompetitive advantages, these potential competitors could reduce our commercial opportunity. Additionally, there currently are, and in the future there maybe, already-approved products for certain of the indications for which we are developing, or in the future may choose to develop, product candidates. Forinstance, PAH is a competitive indication with established products, including other formulations of treprostinil.NTM lung disease competitive overviewIn the NTM lung disease market, our major competitors include pharmaceutical and biotechnology companies that have approved therapies ortherapies in development for the treatment of chronic lung infections. There are other companies that are currently conducting early stage clinical trials forthe treatment of NTM lung disease. We are not aware of any approved inhaled therapies specifically indicated for refractory NTM lung infections in NorthAmerica, Europe or Japan, but, as previously described, there is an ATS/IDSA-recommended treatment regimen that is utilized.Government RegulationOrphan Drug DesignationUnited StatesUnder the Orphan Drug Act (ODA), the FDA may grant orphan drug designation to drugs intended to treat a rare disease or condition, defined as adisease or condition for which the drug is intended affects fewer than 200,000 people in the US, if it meets certain criteria specified by the ODA and FDA.After the FDA grants orphan drug designation, the drug and the specific intended use(s) for which it has obtained designation are listed by the FDA in apublicly-accessible database. The FDA has designated ARIKAYCE as an orphan drug for treatment of (i) infections caused by NTM, (ii) bronchiectasis inpatients with Pseudomonas aeruginosa or other susceptible microbial pathogens and (iii) bronchopulmonary Pseudomonas aeruginosa infections in CFpatients.Orphan drug designation qualifies the sponsor for various development incentives of the ODA, including tax credits for qualified clinical testing,and a waiver of the PDUFA application fee (unless the application seeks approval for an indication not included in the orphan drug designation). Orphandrug designation also affords the company a period of exclusivity for the orphan indication upon approval of the drug. Specifically, the first NDA applicantwith an FDA orphan drug designation for a particular active moiety to receive FDA approval of the drug for an indication covered by the orphan designationis entitled to a seven-year exclusive marketing period, often referred to as orphan drug exclusivity, in the US for that drug in that indication. A product thathas several separate orphan designations may have several separate exclusivities for separate orphan indications. During the orphan drug exclusivity period,the FDA may not approve any other applications to market the same drug for the same indication for use, except in limited circumstances, such as a showingof clinical superiority to the product that has orphan drug exclusivity. Orphan drug exclusivity does not prevent the FDA from approving a different drug forthe same disease or condition or the same drug for a different disease or condition, and it does not alter the timing or scope of the regulatory review andapproval process; the sponsor must still submit evidence from clinical and non-clinical studies sufficient to demonstrate the safety and effectiveness of thedrug.European UnionThe European Commission grants orphan drug designation to promote the development of drugs or biologics (1) for life-threatening or chronicallydebilitating conditions affecting not more than five in 10,000 people in the EU, or (2) for life threatening, seriously debilitating or serious and chroniccondition in the EU where, without incentives, sales of the drug in the European Economic Area (the EU plus Iceland, Lichtenstein, and Norway) (EEA) areunlikely to be sufficient to justify its development. Orphan drug designation is available either if no other satisfactory method of diagnosing, preventing ortreating the condition is approved in the EEA or if such a method does exist but the proposed orphan drug will be of significant benefit to patients. TheEuropean Commission has granted an orphan designation for ARIKAYCE for the treatment of NTM lung disease.If a drug with an orphan drug designation subsequently receives a marketing authorization for a therapeutic indication which is covered by suchdesignation, the drug is entitled to orphan exclusivity. Orphan exclusivity means that the EMA or a national medicines agency may not accept anotherapplication for authorization, or grant an authorization, for a same or similar drug for the same therapeutic indication. Competitors may receive such amarketing authorization despite orphan exclusivity, provided that they demonstrate that the existing orphan product is not supplied in sufficient quantitiesor that the 'second' drug or biologic is clinically superior to the existing orphan product. The 'second' drug may but need not have an15Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentsorphan designation as well. The period of orphan exclusivity is ten years, which can be extended by two years where an agreed pediatric investigation planhas been implemented. The exclusivity period may also be reduced to six years if the designation criteria are no longer met, including where it is shown thatthe product is sufficiently profitable not to justify maintenance of market exclusivity. Each orphan designation carries the potential for one marketexclusivity for all the therapeutic indications that are covered by the designation. A product that has several separate orphan designations may have severalseparate market exclusivities.Orphan drug designation also provides opportunities for free protocol assistance and fee reductions for access to the centralized regulatoryprocedure or fee exemptions for companies with a small and medium enterprises status. In addition, Member States may provide national benefits to orphandrugs, such as early access to the reimbursement procedure or exemption from any turnover tax imposed on pharmaceutical companies.The orphan designation may be applied for at any time during the development of the drug but before the application for marketing authorization.At the time of marketing authorization, the criteria for orphan designation are examined again, and the European Commission decides on the maintenance ofthe orphan designation. The non-maintenance of the orphan designation means that the drug loses its orphan status and thus no longer benefits from orphanexclusivity, fee reductions or exemptions, and national benefits.JapanThe Ministry of Health, Labour and Welfare (MHLW) may, after hearing the opinion of the Pharmaceutical Affairs and Food Sanitation Council,grant orphan drug designation to a drug intended to treat a rare disease or condition if the drug meets the following conditions: (i) the number of targetpatients is less than 50,000 in Japan, (ii) the necessity of orphan drug designation is high from a medical point of view, (iii) there are sufficient theoreticalgrounds to use the drug for the target disease, and (iv) the plan for development of the drug is appropriate. Even if a drug is granted orphan drug designation,however, it does not always receive the manufacturing and marketing approval that is necessary for the drug to be sold or marketed in Japan. ARIKAYCE didnot qualify for orphan drug designation in Japan due to the estimated number of NTM patients in Japan exceeding 50,000.Drug ApprovalUnited StatesIn the US, pharmaceutical products are subject to extensive regulation by the FDA and other government bodies. The US Federal Food, Drug andCosmetic Act (FDCA) and other federal and state statutes and regulations govern, among other things, the research, development, testing, manufacture,storage, recordkeeping, approval, labeling, promotion and marketing, distribution, post-approval monitoring and reporting, sampling and import and exportof pharmaceutical products. Failure to comply with applicable US requirements at any time during product development, approval, or after approval maysubject a company to a variety of administrative or judicial sanctions, such as imposition of clinical holds, FDA refusal to file or approve new drugapplications, warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals ofgovernment contracts, restitution, disgorgement, civil penalties, and criminal prosecution. The description below summarizes the current approval process inthe US for our product and product candidates.Preclinical StudiesPreclinical studies include laboratory evaluation of product chemistry, formulation and toxicity, and pharmacology, as well as animal trials toassess the characteristics and potential safety and efficacy of the product. The conduct of the preclinical tests must comply with federal regulations andrequirements including the FDA's good laboratory practices (GLP) regulations and the US Department of Agriculture's regulations implementing the AnimalWelfare Act. An Investigational New Drug (IND) sponsor must submit the results of the preclinical tests, together with manufacturing information, analyticaldata, any available clinical data or literature, and a proposed clinical trial protocol, among other things, to the FDA as part of an IND application. Certainnon-clinical tests, such as animal tests of reproductive toxicity and carcinogenicity, may continue even after the IND is submitted. An IND automaticallybecomes effective 30 days after receipt by the FDA, unless before that time the FDA raises concerns or questions related to one or more proposed clinicaltrials and places the clinical trial on a clinical hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinicaltrial can begin. As a result, submission of an IND may not result in the FDA allowing clinical trials to commence.Clinical TrialsClinical trials involve the administration of the investigational new drug to human subjects (healthy volunteers or patients) under the supervisionof a qualified investigator. Clinical trials must be conducted (i) in compliance with all applicable federal regulations and guidance, including thosepertaining to good clinical practice (GCP) standards that are meant to protect the rights, safety, and welfare of human subjects and to define the roles ofclinical trial sponsors, investigators, and monitors as well as (ii) under protocols detailing, among other things, the objectives of the trial, the parameters to beused in monitoring16Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentssafety, and the effectiveness criteria to be evaluated. Each protocol involving testing of a new drug in the US (whether in patients or healthy volunteers) mustbe included as a submission to the IND, and the FDA must be notified of subsequent protocol amendments, including new protocols. In addition, the protocolmust be reviewed and approved by an institutional review board (IRB), and all study subjects must provide informed consent. Typically, before any clinicaltrial, each institution participating in the trial will require review of the protocol before the trial commences at that institution. Progress reports detailing theresults of the clinical trials must be submitted at least annually to the FDA and there are additional, more frequent reporting requirements for certain adverseevents.A study sponsor might choose to discontinue a clinical trial or a clinical development program for a variety of reasons. The FDA may impose atemporary or permanent clinical hold, or other sanctions, if it believes that the clinical trial either is not being conducted in accordance with the FDArequirements or presents an unacceptable risk to the clinical trial subjects. An IRB also may require the clinical trial at the site to be halted, either temporarilyor permanently, for failure to comply with the IRB's requirements, or may impose other conditions.Clinical trials to support NDAs for marketing approval are typically conducted in three sequential pre-approval phases, but the phases may overlapor be combined. In Phase 1, short term (typically less than a few months) testing is conducted in a small group of subjects (typically 20-100), who may bepatients with the target disease or condition or healthy volunteers, to evaluate its safety, determine a safe dosage range, and identify side effects. In Phase 2,the drug is given to a larger group of subjects (typically up to several hundred) with the target condition to further evaluate its safety and gather preliminaryevidence of efficacy. Phase 3 studies typically last between several months and two years. In Phase 3, the drug is given to a large group of subjects with thetarget disease or condition (typically several hundred to several thousand), often at multiple geographical sites, to confirm its effectiveness, monitor sideeffects, and collect data to support drug approval. Only a small percentage of investigational drugs complete all three phases of development and obtainmarketing approval.NDAAfter completion of the required clinical testing, an NDA can be prepared and submitted to the FDA. FDA approval of the NDA is required beforemarketing of the product may begin in the US. The NDA is a large submission that must include, among other things, the results of all preclinical, clinical andother testing and a compilation of data relating to the product's pharmacology, chemistry, manufacture, and controls. The application also includesrepresentative samples, copies of the proposed product labeling, patent information, and a financial certification or disclosure statement. The cost ofpreparing and submitting an NDA is substantial. Additionally, under federal law (as amended by the most recent reauthorization of the Prescription Drug UserFee Act (PDUFA VI) in the FDA Reauthorization Act of 2017), most NDAs are subject to a substantial application fee and, upon approval, the applicant willbe assessed an annual prescription drug program fee, both of which are adjusted annually. NDAs for orphan drugs are not subject to an application fee, unlessthe application includes an indication other than the orphan-designated indication. FDA also has the authority to grant waivers of certain user fees, pursuantto the FDCA.The FDA has 60 days from its receipt of an NDA to determine whether the application is accepted for filing based on the FDA's thresholddetermination that it is sufficiently complete to permit substantive review. Once the submission is accepted for filing, the FDA begins a substantive review.The FDA may refer applications for novel drug products or drug products that present difficult questions of safety or efficacy to an advisory committee,typically a panel that includes outside clinicians and other experts, for review, evaluation and a recommendation as to whether the application should beapproved. The FDA is not bound by the recommendation of an advisory committee, but it generally follows such recommendations.Before approving an NDA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP. Additionally, the FDA willtypically inspect the facility or the facilities at which the drug is manufactured. FDA will not approve the product unless compliance with current goodmanufacturing practices (cGMP) is satisfactory and the NDA contains data that provide substantial evidence of effectiveness for the proposed indication,generally consisting of adequate and well-controlled clinical investigations, and that the drug is safe for use under the conditions of use in the proposedlabeling. The FDA also reviews the proposed labeling submitted with the NDA and typically requires changes in the labeling text.After the FDA evaluates the NDA and the manufacturing and testing facilities, it issues either an approval letter or a complete response letter.Complete response letters generally outline the deficiencies in the submission and delineate the additional testing or information needed in order for the FDAto reconsider the application. If and when those deficiencies have been addressed to the FDA's satisfaction in a resubmission of the NDA, the FDA will issuean approval letter. An approval letter, which may specify post approval requirements, authorizes commercial marketing of the drug for the approvedindication or indications and the other conditions of use set out in the approved prescribing information. Once granted, product approvals may be withdrawnif compliance with regulatory standards is not maintained or problems are identified following initial marketing. Under priority review status, the FDA has180 days from either the 60 day filing date (in the case of NME NDA submissions) or the date of receipt of the NDA (in the case of non-NME original NDAsubmissions) to issue either an approval letter or a complete response letter, unless the review period is adjusted by mutual agreement between the FDA andthe17Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentsapplicant or as a result of the applicant submitting a major amendment. The FDA's current performance goals call for the FDA to complete review of90 percent of standard (non-priority) NDAs within 10 months and priority NDAs within six months of NDA filing or receipt.As a condition of NDA approval, the FDA may require substantial post-approval testing, known as phase 4 studies, to be conducted in order togather additional information on the drug's effect in various populations and any side effects associated with long-term use. Beyond routine post marketingsafety surveillance, the FDA may require specific additional surveillance to monitor the drug's safety or efficacy and may impose other conditions, includinglabeling restrictions that can materially affect the potential market and profitability of the drug. As a condition of approval, or after approval, the FDA alsomay require submission of a risk evaluation and mitigation strategy (REMS) or a REMS with elements to assure safe use to mitigate any identified orsuspected serious risks. The REMS may include medication guides, physician communication plans, assessment plans, and elements to assure safe use, suchas restricted distribution methods, patient registries, or other risk minimization tools. Further post-approval requirements are discussed below.Expedited Review and Approval of Eligible DrugsUnder the FDA's accelerated approval program, the FDA may approve certain drugs for serious or life-threatening conditions on the basis of asurrogate or intermediate endpoint that is reasonably likely to predict clinical benefit, which can substantially reduce time to approval. A surrogate endpointused for accelerated approval is a marker—a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinicalbenefit, but is not itself a measure of clinical benefit. An intermediate clinical endpoint is a clinical endpoint that can be measured earlier than irreversiblemorbidity and mortality (IMM) that is reasonably likely to predict an effect on IMM or other clinical benefit. The FDA bases its decision on whether toaccept the proposed surrogate or intermediate clinical endpoint on the scientific support for that endpoint.As a condition of accelerated approval, the FDA typically requires certain post-marketing clinical studies to verify and describe clinical benefit ofthe product, and may impose restrictions on distribution to assure safe use. Post marketing studies would usually be required to be studies already underwayat the time of the accelerated approval. In addition, promotional materials for an accelerated approval drug to be used in the first 120 days post-approval mustbe submitted to the FDA prior to approval, and materials to be used after that 120-day period must be submitted 30 days prior to first use. If the required post-marketing studies fail to verify the clinical benefit of the drug, or if the applicant fails to perform the required post-marketing studies with due diligence, theFDA may withdraw approval of the drug under streamlined procedures in accordance with the agency's regulations. The agency may also withdraw approvalof a drug if, among other things, the promotional materials for the product are false or misleading, or other evidence demonstrates that the drug product is notshown to be safe or effective under its conditions of use.The FDA also has various programs—fast track designation, priority review, and breakthrough designation—that are intended to expedite orstreamline the process for the development and FDA review of drugs that meet certain qualifications. The purpose of these programs is to provide importantnew drugs to patients earlier than under standard FDA review procedures. The programs each have different eligibility criteria and provide different benefits,and can be applied either alone or in combination depending on an applicant's circumstances. Fast track designation applies to a drug that is intended to treata serious condition and for which nonclinical or clinical data demonstrate the potential to address unmet medical need. It should be requested at the time ofIND submission or ideally no later than the pre-NDA meeting. The FDA must respond to requests for fast track designation within 60 days of receipt of therequest. If granted, the applicant is eligible for actions to expedite development and review, such as frequent interaction with the review team, as well as forrolling review, meaning that the applicant may submit sections of the application as they are available. The timing of FDA's review of these sections dependson a number of factors, and the review clock does not start running until the agency has received a complete NDA submission. The FDA may withdraw fasttrack designation if the agency determines that the designation is no longer supported by data emerging in the clinical trial process.Priority review applies to an application (both original and efficacy supplement) for a drug that treats a serious condition and that, if approved,would provide a significant improvement in safety or effectiveness. It also applies to any supplement that proposes a labeling change pursuant to a report ona pediatric study. A request for priority review is submitted at the time of NDA or supplemental NDA submission. The FDA must respond within 60 days ofreceipt of the request. If granted, the review time is shortened from the standard 10 months to 6 months, beginning either at the 60 day filing date (in the caseof NME NDA submissions) or the date of receipt (in the case of non-NME original NDA submissions).Breakthrough therapy designation applies to a drug that is intended to treat a serious condition and for which preliminary clinical evidenceindicates that the drug may demonstrate substantial improvement on a clinically significant endpoint(s) over available therapies. It can be requested with theIND submission and ideally no later than the end-of-phase 2 meeting. The FDA must respond within 60 days of receipt of the request. If granted, the applicantreceives intensive guidance on efficient drug development, intensive involvement of senior managers and experienced review and regulatory health project18Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentsmanagement staff in a proactive, collaborative, cross-disciplinary review, rolling review, and other actions to expedite review. Designation may be rescindedif the product no longer meets the criteria for breakthrough therapy designation.Drugs that are designated as QIDPs are eligible for priority review and fast track designation, and well as market exclusivity. A product is eligible ifit is an antibacterial or anti-fungal drug for human use that is intended to treat serious or life-threatening infections, including: those caused by an anti-bacterial or anti-fungal resistant pathogen, including novel or emerging infectious pathogens; or caused by qualifying pathogens listed by the FDA. A drugsponsor may request that the FDA designate its product as a QIDP at any time prior to NDA submission. The FDA must make a QIDP determination within60 days of receiving the designation request. ARIKAYCE has been designated as a QIDP for NTM lung disease.Additionally, the FDA may approve eligible drugs under the LPAD. A product is eligible if it is intended to treat a serious or life-threateninginfection in a limited population of patients with unmet needs, the drug otherwise meets the standards of approval, and the FDA receives a written requestfrom the sponsor to approve the drug under this pathway. An antibacterial or antifungal drug approved through this pathway may follow a streamlinedclinical development program involving smaller, shorter, or fewer clinical trials. Approval is based on a benefit-risk assessment in the intended limitedpopulation, taking into account the severity, rarity, or prevalence of the infection the drug is intended to treat and the availability or lack of alternativetreatment for the patient population. Such drugs may not have favorable benefit-risk profiles in a broader population. Drugs approved under LPAD aresubject to additional regulatory requirements, including labeling and advertising statements regarding the limited population and submission of promotionalmaterials to the FDA at least 30 days prior to dissemination. The FDA may remove these additional requirements if the agency approves the drug for abroader population.ExclusivitiesAfter NDA approval, owners of relevant drug patents may apply for up to a five-year patent extension on a single patent. The allowable patent termextension is calculated as half of the drug's testing phase (the time between IND application and NDA submission) and all of the review phase (the timebetween NDA submission and approval) up to a maximum of five years. The time can be shortened if the FDA determines that the applicant did not pursueapproval with due diligence. The total patent term after the extension may not exceed 14 years. For patents that might expire during the application phase,the patent owner may request an interim patent extension. An interim patent extension increases the patent term by one year and may be renewed up to fourtimes. For each interim patent extension granted, the post-approval patent extension is reduced by one year. The director of the USPTO must determine thatapproval of the drug covered by the patent for which a patent extension is being sought is likely. Interim patent extensions are not available for a drug forwhich an NDA has not been submitted.A variety of non-patent exclusivity periods are available under the FDCA that can delay the submission or approval of certain applications forcompeting products.A five-year period of non-patent exclusivity within the US is granted to the first applicant to gain approval of an NDA for a new chemical entity(NCE). An NCE is a drug that contains no active moiety (the molecule or ion responsible for the action of the drug substance) that has been approved by theFDA in any other application submitted under section 505(b) of the FDCA. During the exclusivity period for a NCE, the FDA may not accept for review anabbreviated new drug application, or ANDA, or a 505(b)(2) NDA submitted by another company that references (i.e., relies on FDA prior approval of) the NCEdrug. However, an ANDA or 505(b)(2) NDA may be submitted after four years if it contains a certification of patent invalidity or non-infringement withrespect to a patent listed with the FDA for the reference NDA.A three-year period of non-patent exclusivity is granted for a drug product that contains an active moiety that has been previously approved, whenthe application contains reports of new clinical investigations (other than bioavailability studies) conducted or sponsored by the sponsor that were essentialto approval of the application, for example, for new indications, dosages, strengths or dosage forms of an existing drug. This three-year exclusivity coversonly the conditions of use associated with the new clinical investigations, which means that the FDA may approve applications for other versions of theoriginal, unmodified drug product. Where this form of exclusivity applies, it prevents FDA approval of an ANDA or 505(b)(2) NDA subject to the exclusivityfor the three-year period; however, the FDA may accept and review ANDAs or 505(b)(2) NDAs during the three-year period.These exclusivities also do not preclude FDA approval of a 505(b)(1) application for a duplicate version of the drug during the period ofexclusivity, provided that the applicant conducts or obtains a right of reference to all of the preclinical studies and adequate and well-controlled clinicaltrials necessary to demonstrate safety and effectiveness.Products with QIDP designation may receive a five-year extension of other non-patent exclusivities for which the drug is also eligible. Theexclusivity does not prevent the FDA from approving a subsequent application for a change to the QIDP-designated drug that results in a new indication,route of administration, dosing, schedule, dosage form, delivery system, delivery device or strength. For example, a drug that has been designated as both anorphan drug and a QIDP for the same indication, like ARIKAYCE, could be eligible for a combined 12 years of exclusivity for that indication.19Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsMedical Device RegulationMedical devices, such as the Lamira Nebulizer System, may receive marketing authorization from the FDA as stand-alone devices, or in some cases,may receive marketing authorization as part of a combination product. In either case, the ultimate product will need to satisfy FDA requirements. The primarypathways for marketing authorization for devices in the US are 510(k) clearance or premarket approval (PMA).Medical devices are also subject to certain post-clearance, post-approval requirements. Those requirements include continuing Quality SystemRegulation compliance, Medical Device Reporting, Correction and Removal, and requirements governing labeling and promotional advertising.The FDCA permits medical devices intended for investigational use to be shipped to clinical sites if such devices comply with prescribedprocedures and conditions. Devices intended for investigational use may be exempted from premarket notification and premarket approval requirementswhen shipped for use in clinical trials, but they must bear a label indicating that they are for investigational use. This labeling may not represent that thedevice is safe or effective for the purposes for which it is being investigated.Combination ProductsA combination product is a product comprising two or more regulated components (e.g., a drug and device) that are combined into a singleproduct, co-packaged, or sold separately but intended for co-administration, as evidenced by the labeling for the products. Drugs that are administered usinga nebulizer or another device, such as ARIKAYCE or INS1009, are examples of combination drug/device products.The FDA is divided into various Centers, which each have authority over a specific type of product. NDAs are reviewed by personnel within theCenter for Drug Evaluation and Research, while device applications and premarket notifications are reviewed by the Center for Devices and RadiologicalHealth. Combination products, such as drug/device combinations, generally will be reviewed by the Center that regulates the product's primary mode ofaction (PMOA), which is the single mode of a combination product that provides the most important therapeutic action of the combination product. If thePMOA is unclear or in dispute, a sponsor may file a Request for Designation with FDA’s Office of Combination Products (OCP), which will render adetermination and assign a lead Center. OCP generally assigns jurisdiction based on PMOA. If there are two independent modes of action, neither of which issubordinate to the other, the FDA makes a determination as to which Center to assign the product based on consistency with other combination productsraising similar types of safety and effectiveness questions or to the Center with the most expertise in evaluating the most significant safety and effectivenessquestions raised by the combination product.When evaluating an application for a combination product, a lead Center may consult other Centers and apply the standards that would beapplicable but still retain reviewing authority, or it may assign review of a specific section of the application to another Center, delegating its reviewauthority for that section. Depending on the type of combination product, approval or clearance could be obtained through submission of a single marketingapplication or through separate applications for the individual constituent parts (e.g., an NDA for the drug and a premarket notification for the device). TheFDCA directs the FDA to conduct a review of a combination product under a single marketing application whenever appropriate. The agency has thediscretion to require separate applications to more than one Center, and applicants may choose to submit separate applications for constituent parts of acombination (unless the FDA determines one application is necessary). One reason to submit multiple applications is if the applicant wishes to receive somebenefit that accrues only from approval under a particular type of application, like new drug product exclusivity. If multiple applications are submitted, eachapplication is generally reviewed by the Center with authority over each application type. For combination products that contain an approved constituentpart (such as a drug-device combination product in which the device has previously received clearance), the FDA may require that the application(s) includeonly such information as is necessary to meet the standard for clearance or approval, taking into account any prior finding of safety or effectiveness for theapproved constituent part.Like their constituent products—e.g., drugs and devices—combination products are highly regulated and subject to a broad range of postmarketing requirements including cGMPs, adverse event reporting, periodic reports, labeling and advertising and promotion requirements and restrictions.Disclosure of Clinical Trial InformationUnder US and certain foreign laws intended to improve clinical trial transparency, sponsors of clinical trials may be required to register anddisclose certain information about their clinical trials. This can include information related to the investigational drug, patient population, phase ofinvestigation, study sites and investigators, and other aspects of the clinical trial. This information is then made publicly available. Under a recently revisedregulation in the US, sponsors are obligated to disclose the results of these trials after completion (prior to the new rulemaking, disclosure of results was onlyrequired if the product or new indication was approved by the FDA). In the US, disclosure of the results of these trials can be delayed for up20Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentsto two years if the sponsor is seeking approval of the product or a new indication. Competitors may use this publicly-available information to gainknowledge regarding the progress of development programs.Other Post-approval Regulatory RequirementsOnce an NDA is approved, a product will be subject to certain post-approval requirements, including those relating to advertising, promotion,adverse event reporting, recordkeeping, and cGMP, as well as registration, listing, and inspection. There also are continuing, annual user fee requirements, aswell as new application fees for supplemental applications with clinical data.The FDA regulates the content and format of prescription drug labeling, advertising, and promotion, including direct-to-consumer advertising andpromotional Internet communications. FDA also establishes parameters for permissible non-promotional communications between industry and the medicalcommunity, including industry-supported scientific and educational activities. The FDA and other agencies actively enforce the laws and regulationsprohibiting the promotion for uses not consistent with the approved labeling, and a company that is found to have improperly promoted off-label uses orotherwise not to have met applicable promotion rules may be subject to significant liability under both the FDCA and other statutes, including the FalseClaims Act.Manufacturers are subject to requirements for adverse event reporting and submission of periodic reports following FDA approval of an NDA.All aspects of pharmaceutical manufacture must conform to cGMPs after approval. Drug manufacturers and certain of their subcontractors arerequired to register their establishments with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA duringwhich the FDA inspects manufacturing facilities to assess compliance with cGMPs. Changes to the manufacturing process are strictly regulated and oftenrequire prior FDA approval before being implemented. FDA regulations also require investigation and correction of any deviations from cGMP and imposereporting and documentation requirements upon the sponsor and any third-party manufacturers that the sponsor may decide to use. Accordingly,manufacturers must continue to expend time, money and effort in the areas of production and quality control to maintain compliance with cGMPs.Drugs may be marketed only for the approved indications and in accordance with the provisions of the approved labeling. Changes to some of theconditions established in an approved application, including changes in indications, labeling, product formulation, or manufacturing processes or facilities,require submission and FDA approval of a new NDA or NDA supplement, in some cases before the change may be implemented. An NDA supplement for anew indication typically requires clinical data similar to that in the original application, and the FDA uses the same procedures and actions in reviewing NDAsupplements as it does in reviewing NDAs.As previously mentioned, the FDA also may require phase 4 studies and may require a REMS, which could restrict the distribution or use of theproduct.In addition, the distribution of prescription pharmaceutical products is subject to the Prescription Drug Marketing Act (PDMA), which regulatesthe distribution of drugs and drug samples at the federal level, and sets minimum standards for the registration and regulation of drug distributors by thestates. Both the PDMA and state laws limit the distribution of prescription pharmaceutical product samples and impose requirements to ensure accountabilityin distribution.European UnionMAATo obtain approval of a drug under the EU regulatory system, an application for a marketing authorization may be submitted under a centralized, adecentralized or a national procedure. The centralized procedure, which is compulsory for medicines produced by certain biotechnological processes or fororphan drugs, provides for the grant of a single marketing authorization that is valid for all EU member states, which grants the same rights and obligations ineach member state as a national marketing authorization. As a general rule, only one marketing authorization may be granted for drugs approved through thecentralized procedure and the marketing authorization is also relevant for the EEA countries.Under the centralized procedure, the Committee for Medicinal Products for Human Use (CHMP) is required to adopt an opinion on a validapplication within 210 days, excluding clock stops when additional information is to be provided by the applicant in response to questions. Morespecifically, on day 120 of the procedure, once the CHMP has received the preliminary assessment reports and opinions from the Rapporteur and Co-Rapporteur designated by the CHMP, it adopts a list of questions, which are sent to the applicant together with the CHMP's overall conclusions. Applicantsthen have three months to respond to the CHMP (and can request a three-month extension). The Rapporteur and Co-Rapporteur assess the applicant's replies,revise the assessment report as necessary and may prepare a list of outstanding issues. The revised assessment report and list of outstanding issues are sent tothe applicant together with the CHMP's recommendation by day 180 of the procedure. Applicants then have one month to respond to the CHMP (and canrequest a one or two-month extension). The Rapporteur and21Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsCo-Rapporteur assess the applicant's replies, submit them for discussion to the CHMP and prepare a final assessment report. Once its scientific evaluation iscompleted, the CHMP gives a favorable or unfavorable opinion as to whether to grant the marketing authorization. After the adoption of the CHMP opinion,a decision must be adopted by the European Commission, after consulting the Standing Committee of the Member States. The European Commissionprepares a draft decision and circulates it to the member states; if the draft decision differs from the CHMP opinion, the Commission must provide detailedexplanations. The European Commission adopts a decision within 15 days of the end of the consultation procedure.Accelerated Procedure, Conditional Approval and Approval Under Exceptional CircumstancesVarious programs, including accelerated procedure, conditional approval and approval under exceptional circumstances, are intended to expediteor simplify the approval of drugs that meet certain qualifications. The purpose of these programs is to provide important new drugs to patients earlier thanunder standard approval procedures.For drugs which are of major interest from the point of view of public health, in particular from the viewpoint of therapeutic innovation, applicantsmay submit a substantiated request for accelerated assessment. If the CHMP accepts the request, the review time is reduced from 210 to 150 days.Furthermore, for certain categories of medicinal products, marketing authorizations may be granted on the basis of less complete data than isnormally required in order to meet unmet medical needs of patients or in the interest of public health. In such cases, the company may request, or the CHMPmay recommend, the granting of a marketing authorization, subject to certain specific obligations; such marketing authorization may be conditional or underexceptional circumstances. The timelines for the centralized procedure described above also apply with respect to applications for a conditional marketingauthorization or marketing authorization under exceptional circumstances.Conditional marketing authorizations may be granted for products designated as orphan medicinal products, if all of the following conditions aremet: (1) the risk-benefit balance of the product is positive, (2) the applicant will likely be in a position to provide the required comprehensive clinical trialdata, (3) the product fulfills unmet medical needs, and (4) the benefit to public health of the immediate availability on the market of the medicinal productconcerned outweighs the risk inherent in the fact that additional data are still required.Conditional marketing authorizations are valid for one year, on a renewable basis until the holder provides a comprehensive data package. Thegranting of conditional marketing authorization depends on the applicant's ability to fulfill the conditions imposed within the agreed upon deadline. Theyare subject to "conditions", i.e. the holder is required to complete ongoing studies or to conduct new studies with a view to confirming that the benefit-riskbalance is positive or to fulfill specific obligations in relation to pharmacovigilance. Once the holder has provided a comprehensive data package, theconditional marketing authorization is replaced by a 'regular' marketing authorization.Marketing authorizations under exceptional circumstances may be granted where the applicant demonstrates that, for objective and verifiablereasons, they are unable to provide comprehensive data on the efficacy and safety of the drug under normal conditions of use. Such marketing authorizationsare subject to certain conditions, in particular relating to safety of the drug, notification of incidents relating to its use or actions to be taken. They are validfor an indefinite period of time, but the conditions upon which they are based are subject to an annual reassessment in order to ensure that the risk-benefitbalance remains positive.ExclusivitiesIf an approved drug contains a new active substance, it is protected by data exclusivity for eight years from the notification of the Commissiondecision granting the marketing authorization and then by marketing protection for an additional two or three years. Overall, the drug is protected for ten oreleven years against generic competition, and no additional exclusivity protection is granted for any new development of the active substance it contains.During the eight-year period of data exclusivity, competitors may not refer to the marketing authorization dossier of the approved drug forregulatory purposes. During the period of marketing protection, competitors may not market their generic drugs. The period of marketing protection isnormally two years but may become three years if, during the eight-year data exclusivity period, a new therapeutic indication is approved that is consideredas bringing a significant clinical benefit over existing therapies.Medical Devices RegulationsIn the EU, the marketing of medical devices is not subject to a prior approval by a health authority, but, depending on the class of device, mayrequire prior review by a Notified Body. Notified Bodies are technical review bodies that are accredited and supervised by national health authorities. Theyconduct conformity assessment procedures of, among others, medical devices.22Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsMedical devices are generally governed by Directive 93/42/EEC on Medical Devices that harmonizes the conditions for placing medical deviceson the European market. This Directive however does not regulate certain important marketing aspects, such as advertising or pricing and reimbursement,which remain governed by national law.Directive 93/42 requires medical devices to meet the essential requirements which are enumerated in the annexes to the Directive. Compliancewith those requirements is demonstrated by the CE mark as the manufacturer may only affix the CE mark if it may declare conformity with the essentialrequirement for each medical device that is marketed. Directive 93/42 provides recourse to harmonized European standards in order to facilitate compliancewith the essential requirements. Harmonized standards provide a presumption of conformity with the essential requirements.Directive 93/42 institutes several conformity assessment procedures. The relevant conformity assessment procedure depends on the type of medicaldevice and the risks involved. Devices are divided in four groups: Class I, Class IIa, Class IIb, and Class III. Class I devices present the lowest level of risk sothat, for most of these devices the manufacturer can self-certify the product and need not rely on certification by a Notified Body. For the other classes, aNotified Body must review the manufacturer's procedures and/or the product. Every device is initially classified by the manufacturer. However, the NotifiedBody may dispute the classification and assert that the device should be included in a class requiring stricter conformity assessment procedures. Specificrules apply to custom-made medical devices, medical devices that are used in clinical trials, and medical devices that incorporate a medicinal ingredient.For classes of devices other than Class I, a manufacturer must have a Notified Body test and certify conformity of its design and productionprocedures or its products with the essential requirements of Directive 93/42. Certification takes the form of a certificate of conformity issued by the NotifiedBody, which is valid throughout the European Union. Upon certification by the Notified Body, the manufacturer affixes the CE mark to the medical device,which allows the product to move freely within the EU and thus prevents EU Member States from restricting sales and marketing of the devices, unless suchmeasure is justified on the basis of evidence of non-compliance. Ultimately, the manufacturer is responsible for the conformity of the device with theessential requirements and for the affixing of the CE mark. The Lamira Nebulizer System is CE marked by PARI in the EU.Manufacturers of medical devices are subject to materiovigilance obligations that require reporting of incidents or near incidents related to the useof a medical device, which incidents may demonstrate the need for corrective action by the manufacturer. In addition, Notified Bodies regularly re-assess theconformity of a medical device to the essential requirements of Directive 93/42 and may from time to time audit the manufacturer and may, where needed,suspend or withdraw the manufacturer's certificate of conformity.In May 2017, the EU adopted a new Medical Devices Regulation (EU) 2017/745 (MDR), which will repeal and replace Directive 93/42 with effectfrom May 26, 2020. The MDR envisages, among other things, stricter controls of medical devices, including strengthening of the conformity assessmentprocedures, increased expectations as regards clinical data for devices and pre-market regulatory review of high-risk devices. Under transitional provisions,medical devices with notified body certificates issued under Directive 93/42 prior to May 26, 2020 may continue to be placed on the market for theremaining validity of the certificate, until May 27, 2024 at the latest. After the expiry of any applicable transitional period, only devices that have been CEmarked under the MDR may be placed on the market in the EU.JapanUnder the Japanese regulatory system administered by the MHLW and the PMDA (which is responsible for product review and evaluations under thesupervision of the MHLW), pre-marketing approval and clinical studies are required for all pharmaceutical products. The Law on Securing Quality, Efficacyand Safety of Products Including Pharmaceuticals and Medical Devices (Act No. 145 of 1960) requires a license for marketing authorization when importingto Japan and selling pharmaceutical products manufactured in other countries. It also requires a foreign manufacturer to get each of its manufacturing sitescertified as a manufacturing site of pharmaceutical products to be marketed in Japan. To receive a license for marketing authorization, the manufacturer orseller must, at the very least, employ certain manufacturing marketing, quality and safety personnel. A license for marketing authorization may not be grantedif the quality management methods and post marketing safety management methods applied with respect to the pharmaceutical product fail to conform to thestandards stipulated in the ordinances promulgated by the MHLW. To obtain manufacturing/marketing approval for a new product, a Company must submitan application for approval to the MHLW with results of nonclinical and clinical studies to show the quality, efficacy and safety of the product candidate. Adata compliance review, on-site inspection for good clinical practice, audit and detailed data review for compliance with current good manufacturingpractices are undertaken by the PMDA. The application is then discussed by the committees of the Pharmaceutical Affairs and Food Sanitation Council.Based on the results of these reviews, the final decision on approval is made by the MHLW. The time required for the approval process varies depending onthe product, but it can take years. The product also needs approval for pricing to be applied for redemption of health insurance. The medical products whichonce are approved and marketed are also subject to regular post-marketing vigilance of safety and quality under the standards of Good ManufacturingPractice. In Japan, the National Health Insurance23Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentssystem maintains a Drug Price List specifying which pharmaceutical products are eligible for reimbursement, and the MHLW sets the prices of the productson this list. After receipt of marketing approval, negotiations regarding the reimbursement price with the MHLW would begin. Price would be determinedwithin 60 to 90 days unless the applicant disagrees, which may result in extended pricing negotiations. The government generally introduces price cutrounds every other year and also mandates price decreases for specific products. New products judged innovative or useful, that are indicated for pediatricuse, or that target orphan or small population diseases, however, may be eligible for a pricing premium. The government has also promoted the use ofgenerics, where available.Pediatric InformationUnited StatesUnder the Pediatric Research Equity Act of 2003 (PREA), certain NDAs and supplements must contain data that are adequate to assess the safetyand effectiveness of the drug for the claimed indications in relevant pediatric subpopulations and to support dosing and administration for each pediatricsubpopulation for which the drug is safe and effective. The FDA may, on its own initiative or at the request of an applicant, grant deferrals for submission ofdata or full or partial waivers. Unless otherwise required by regulation, and subject to an exception for certain oncology drugs, PREA does not apply to anydrug for an indication for which orphan designation has been granted. Under the Best Pharmaceuticals for Children Act (BPCA), pediatric research isincentivized by the possibility of six additional months of pediatric exclusivity, which if granted, is added to existing exclusivity periods and patent-basedexclusivity listed for the applicable drug in the FDA's Orange Book at the time the sponsor satisfies the FDA's "written request" for pediatric research.Sponsors may seek to negotiate the terms of a written request during drug development. While the sponsor of an orphan designated drug may not be requiredto perform pediatric studies under PREA unless one of the above exceptions applies, they are eligible to participate in the incentives under the BPCA if theFDA issues a written request.European UnionIn the EU, new drugs (i.e. drugs containing a new active substance) for adults, must also be tested in children. This mandatory pediatric testing iscarried out through the implementation of a pediatric investigation plan, or PIP, which is proposed by the applicant and approved by the EMA. A PIPcontains all the studies to be conducted and measures to be taken in order to support the approval of the new drug, including pediatric pharmaceutical forms,in all subsets of the pediatric population. Validation of the MAA for adults is subject to the implementation of the PIP, subject to one or more waivers ordeferrals. On the one hand, the PIP may allow a deferral for one or more of the studies or measures included therein in order not to delay the approval of thedrug in adults, and, on another hand, the EMA may grant either a product-specific waiver for the (adult) disease/condition or one or more pediatric subsets ora class waiver for the disease/condition. PIPs are subject to modifications from time to time, when they no longer are workable. Prior to obtaining thevalidation of a MAA for adults, the applicant has to demonstrate compliance with the PIP at the time of submission of the application. In the case of orphanmedicinal products, completion of an approved PIP can result in an extension of the market exclusivity period from ten to twelve years.JapanIn Japan, there is no statutory rule which imposes any obligation on pharmaceutical manufacturers engaging in pediatric drug development.However, the guidelines of the MHLW (Handling of Pharmaceuticals during the Reexamination Interval Period (Issue No. 107, February 1, 1999 and No.1324, December 27, 2000)) state as follows: (i) since information on pediatric patients obtained in clinical trials may be limited, the MHLW recommends thatpharmaceutical manufacturers conduct adequate post-marketing surveillance during the reexamination interval period and collect as much information aspossible for proper use of drugs for pediatric patients; and (ii) if a pharmaceutical manufacturer plans to conduct a clinical trial to set the dose of a pediatricdrug to prepare application for manufacturing/marketing approval or after receiving the same approval, the reexamination interval period may be extendedup to 10 years. In addition, since 2010 the MHLW has been promoting the development of children’s drugs that have been approved for use in Europe andthe US but are not yet approved in Japan, so that they can be used as early as possible in Japan as well.Regulation Outside the US, Europe and JapanIn addition to regulations in the US, Europe and Japan, we will be subject to a variety of regulations in other jurisdictions governing clinicalstudies of our candidate products, including medical devices. Regardless of whether we obtain FDA approval for a product candidate, we must obtainapproval of the product candidate (including a medical device) by the comparable regulatory authorities of countries outside the US before we cancommence clinical studies or marketing of the product candidate in those countries. The requirements for approval and the approval process vary fromcountry to country, and the time may be longer or shorter than that required for FDA approval. Under certain harmonized medical device approval/clearanceregulations outside the US, reference to US clearance permits fast-tracking of market clearance. Other regions are harmonized with EU standards, and thereforerecognize the CE mark as a declaration of conformity to applicable standards.24Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsFurthermore, we must obtain any required pricing approvals in addition to regulatory approval prior to launching a product candidate in the approvingcountry.Early Access ProgramsUnder EU law, member states are authorized to adopt national legal regimes for the supply or use of non-authorized drugs in case of therapeuticneeds. The most common national legal regimes are compassionate use programs and named patient sales, but other national regimes for early access may beavailable, depending on the member state. For drugs that must be approved through the centralized procedure, such as orphan drugs, compassionate useprograms are also regulated at the European level. ARIKAYCE is available in certain countries under early access programs.Special programs can be set up to make available to patients with an unmet medical need a promising drug which has not yet been authorized fortheir condition (compassionate use). As a general rule, compassionate use programs can only be put in place for drugs or biologics that are expected to helppatients with life-threatening, long-lasting or seriously disabling illnesses who currently cannot be treated satisfactorily with authorized medicines, or whohave a disease for which no medicine has yet been authorized. The compassionate use route may be a way for patients who cannot enroll in an ongoingclinical trial to obtain treatment with a potentially life-saving medicine. Compassionate use programs are coordinated and implemented by the EU memberstates, which decide independently how and when to open such programs according to national rules and legislation. Generally, doctors who wish to obtain apromising drug for their seriously ill patients will need to contact the relevant national authority in their respective country and follow the procedure that hasbeen set up. Typically, the national authority keeps a register of the patients treated with the drug within the compassionate use program, and a system is inplace to record any side effects reported by the patients or their doctors. Orphan drugs very often are subject to compassionate use programs due to their verynature (rare diseases are life-threatening, long-lasting or seriously disabling diseases) and the long time required for both their approval and effectivemarketing.Doctors can also obtain certain drugs for their patients by requesting a supply of a drug from the manufacturer or a pharmacist located in anothercountry, to be used for an individual patient under their direct responsibility. This is often called treatment on a 'named-patient basis' and is distinct fromcompassionate use programs. In this case, the doctor responsible for the treatment will either contact the manufacturer directly or issue a prescription to befulfilled by a pharmacist. While manufacturers or pharmacists do record what they supply, there is no central register of the patients that are being treated inthis way.Reimbursement of Pharmaceutical ProductsIn the US, many independent third-party payors, as well as the Medicare and state Medicaid programs, reimburse dispensers of pharmaceuticalproducts. Medicare is the federal program that provides health care benefits to senior citizens and certain disabled and chronically ill persons. Medicaid is theneed-based federal and state program administered by the states to provide health care benefits to certain persons.As one of the conditions for obtaining Medicaid and, if applicable, Medicare Part B coverage for our marketed pharmaceutical products, we willneed to agree to pay a rebate to state Medicaid agencies that provide reimbursement for those products. We will also have to agree to sell our commercialproducts under contracts with the Department of Veterans Affairs, Department of Defense, Public Health Service, and numerous other federal agencies as wellas certain hospitals that are designated by federal statutes to receive drugs at prices that are significantly below the price we charge to commercialpharmaceutical distributors. These programs and contracts are highly regulated and will impose restrictions on our business. Failure to comply with theseregulations and restrictions could result in adverse consequences such as civil money penalties, imposition of a Corporate Integrity Agreement and/or a lossof our ability to continue receiving Medicare and Medicaid reimbursement for our drugs. In January 2019, the Department of Health and Human Servicesreleased a proposed rule to reform the system of rebates paid to Medicare Part D plans, Medicaid managed care organizations and pharmacy benefit managers.We are currently reviewing the proposed rule, the impact of which is uncertain at this time.Private healthcare payors also attempt to control costs and influence drug pricing through a variety of mechanisms, including through negotiatingdiscounts with the manufacturers and through the use of tiered formularies and other mechanisms that provide preferential access to certain drugs over otherswithin a therapeutic class. payors also set other criteria to govern the uses of a drug that will be deemed medically appropriate and therefore reimbursed orotherwise covered.The US President has indicated an interest in taking steps to lower drug prices, such as having the federal government negotiate drug prices withpharmaceutical manufacturers and/or in indexing certain federally reimbursement payments to international drug prices. In May 2018, the Administrationissued "American Patients First," a multi-faceted blueprint to lower drug prices. The Administration has taken administrative steps to implement theblueprint, including through proposing sweeping demonstration projects aimed at putting downward pressure on drug prices. In addition, members ofCongress have indicated an interest in legislative measures designed to lower drug costs. Drug pricing is an active area for25Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentsregulatory reform at both the federal and state levels, and significant changes to current drug pricing and reimbursement structures in the US could beforthcomingDifferent pricing and reimbursement schemes exist in other countries. In the EU, governments influence the price of drugs through their pricing andreimbursement rules and control of national health care systems that fund a large part of the cost of those products to patients. Some jurisdictions operatepositive and negative list systems under which drugs may only be marketed once a reimbursement price has been agreed. To obtain reimbursement or pricingapproval, some of these countries may require the completion of clinical trials that compare the cost-effectiveness of a particular drug candidate to currentlyavailable therapies. Other member states allow companies to fix their own prices for drugs, but monitor and control company profits. The downward pressureon health care costs in general, particularly prescription drugs, has become very intense. As a result, increasingly high barriers are being erected to the entryof new drugs. In addition, in some countries, cross-border imports from low-priced markets exert a commercial pressure on pricing within a country. There canbe no assurance that any country that has price controls or reimbursement limitations for drugs will allow favorable reimbursement and pricing arrangementsfor any of our products.In Japan, drugs can be sold on the market if they undergo the PMDA’s review of safety, effectiveness and quality and receivemanufacturing/marketing approval. However, in order for drugs to be covered by the National Health Insurance, they must be included in a Drug Price List.The "Drug Pricing Organization," which is a division of the Central Social Insurance Medical Council (CSIMC), calculates the price of drugs, the generalmeeting of the CSIMC approves the calculated price, and the MHLW includes the drugs and the calculated price in the Drug Price List. After receivingmanufacturing/marketing approval, drugs are included in the Drug Price List within 60 to 90 days unless the applicant disagrees, which may result inextended pricing negotiations. The MHLW updates the Drug Price List biennially after taking into account the survey result of the actual sales price of drugsand hearing the opinion of the CSIMC.Fraud and Abuse and Other LawsPhysicians and other healthcare providers and third-party payors (government or private) often play a primary role in the recommendation andprescription of health care products. In the US and most other jurisdictions, numerous detailed requirements apply to government and private health careprograms, and a broad range of fraud and abuse laws, transparency laws, and other laws are relevant to pharmaceutical companies. US federal and statehealthcare laws and regulations in these areas include the following:•The federal anti-kickback statute;•The federal civil False Claims Act;•The federal Health Insurance Portability and Accountability Act of 1996 (HIPAA), as amended by the Health Information Technology for Economicand Clinical Health Act;•The federal criminal false statements statute;•The price reporting requirements under the Medicaid Drug Rebate Program and the Veterans Health Care Act of 1992;•The federal Physician Payment Sunshine Act, being implemented as the Open Payments Program; and•Analogous and similar state laws and regulations.Similar restrictions apply in the member states of the EU and Japan, which have been set out by laws or industry codes of conduct.EmployeesAs of December 31, 2018, we had a total of 373 employees, including: 130 in research, clinical, regulatory, medical affairs and quality assurance;31 in technical operations, manufacturing and quality control; 84 in general and administrative functions; and 128 in commercial activities. We had 339employees in the US, 28 employees in Europe and 6 employees in Japan. We anticipate increasing our headcount in 2019.None of our employees are represented by a labor union and we believe that our relations with our employees are generally good. Generally, ouremployees are at-will employees; however, we have entered into employment agreements with certain of our executive officers.Available InformationWe file electronically with the SEC our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K, andamendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934 (Exchange Act). We make availableon our website at http://www.insmed.com, free of charge, copies of these reports as soon as reasonably practicable after filing, or furnishing them to, the SEC.The public can also obtain materials that we file with the SEC through the SEC's website at http://www.sec.gov.Also available through our website's "Investor Relations Corporate Governance" page are charters for the Audit, Compensation and Nominationsand Governance Committees of our board of directors, our Corporate Governance Guidelines,26Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentsand our Code of Business Conduct and Ethics. We intend to satisfy the disclosure requirements regarding any amendment to, or waiver from, a provision ofthe Code of Business Conduct and Ethics by making disclosures concerning such matters available on our website.The references to our website and the SEC's website are intended to be inactive textual references only. Neither the information in or that can beaccessed through our website, nor the contents of the SEC's website, are incorporated by reference in this Annual Report on Form 10-K.Financial InformationThe financial information required under this Item 1 is incorporated herein by reference to Item 8 of this Annual Report on Form 10-K.27Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsITEM 1A. RISK FACTORSOur business is subject to substantial risks and uncertainties. Any of the risks and uncertainties described below, either alone or taken together,could materially and adversely affect our business, financial condition, results of operations, prospects for growth, and the value of an investment in ourcommon stock. In addition, these risks and uncertainties could cause actual results to differ materially from those expressed or implied by forward-lookingstatements contained in this Annual Report on Form 10-K (please read the Cautionary Note Regarding Forward-Looking Statements appearing at thebeginning of this Annual Report on Form 10-K).Risks Related to the Commercialization and Continued Approval of ARIKAYCEOur prospects are highly dependent on the success of our only approved product, ARIKAYCE, which was approved in the United States (US) under theLimited Population Pathway for Antibacterial and Antifungal Drugs (LPAD) and accelerated approval pathways. If we are unable to successfullycommercialize or maintain approval for ARIKAYCE, our business, financial condition, results of operations and prospects and the value of our commonstock will be materially adversely affected.Our long-term viability and growth depend on the successful commercialization of ARIKAYCE, our only approved product, which has beenapproved in the US for the treatment of patients with refractory MAC lung disease as part of a combination antibacterial drug regimen for adult patients withlimited or no alternative treatment options. We have invested and continue to invest significant efforts and financial resources in the launch of ARIKAYCE,and our ability to generate revenue from ARIKAYCE will depend heavily on successfully commercializing and obtaining full regulatory approval forARIKAYCE by conducting an appropriate confirmatory post-marketing study. ARIKAYCE is our first commercial launch, and its successfulcommercialization and our receipt of full regulatory approval for ARIKAYCE in the US are subject to many risks.The commercial success of ARIKAYCE will depend on the degree of market acceptance by physicians, patients, third-party payors and others in the healthcare community.Despite receiving US Food and Drug Administration (FDA) approval of ARIKAYCE, the product may not gain, or over time may not retain, marketacceptance by physicians, patients, third-party payors or others in the health care community. ARIKAYCE was the first product approved via the LPADpathway, and there is limited information on how this approval may impact market acceptance of the product. If ARIKAYCE does not achieve and maintainan adequate level of acceptance, it is likely that we will not generate significant revenue or become profitable. The degree of market acceptance ofARIKAYCE, which we launched in the US early in the fourth quarter of 2018, is also dependent on a number of additional factors, including the following:•The willingness of the target patient population to use, and of physicians to prescribe, ARIKAYCE;•The efficacy and potential advantages of ARIKAYCE over alternative treatments;•The risk and safety profile of ARIKAYCE, including, among other things, physician and patient concern regarding the boxed warning and othersafety precautions resulting from its association with an increased risk of respiratory adverse reactions, and any adverse safety information thatbecomes available as a result of longer-term use of ARIKAYCE;•Relative convenience and ease of administration;•The ability of the patient to tolerate ARIKAYCE;•The pricing of ARIKAYCE;•The ability and willingness of the patient to pay out of pocket costs for ARIKAYCE, for example, co-payments;•Sufficient third-party insurance coverage and reimbursement;•The strength of marketing and distribution support and timing of market introduction of competitive products and treatments; and•Publicity concerning ARIKAYCE or any potential competitive products and treatments.Our efforts to educate physicians, patients, third-party payors and others in the health care community on the benefits of ARIKAYCE will requiresignificant resources, which may be greater than those required to commercialize more established technologies and may never be successful.We obtained regulatory approval of ARIKAYCE in the US through an accelerated approval process, and full approval will be contingent on successfulcompletion of a confirmatory post-marketing study. Failure to obtain full approval or otherwise meet our post-marketing requirements and commitmentswould have a material adverse effect on our business.The FDA approved ARIKAYCE under the LPAD and accelerated approval pathways, and full approval will be based on results from a post-approvalconfirmatory clinical trial. Accelerated approval allows drugs that (i) are being developed to28Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentstreat a serious or life-threatening disease or condition and (ii) provide a meaningful therapeutic benefit over existing treatments to be approved substantiallybased on an intermediate endpoint or a surrogate endpoint that is reasonably likely to predict clinical benefit, rather than a clinical endpoint such as survivalor irreversible morbidity. Accelerated approval of ARIKAYCE was supported by preliminary data from the Phase 3 CONVERT study, which evaluated thesafety and efficacy of ARIKAYCE in adult patients with refractory MAC lung disease, using achievement of sputum culture conversion (defined as threeconsecutive negative monthly sputum cultures) by Month 6 as the primary endpoint.The required confirmatory trial, which is currently under discussion with FDA, is proposed to be a randomized, double-blind, placebo-controlledclinical trial to assess and describe the clinical benefit of ARIKAYCE in patients with MAC lung disease. The trial will evaluate the effect of ARIKAYCE ona clinically meaningful endpoint, as compared to an appropriate control in the intended patient population of patients with MAC lung disease. Pursuant tothe timetable agreed upon with the FDA, the study protocol is scheduled to be finalized during the first half of 2019, with trial results to be reported by 2024.There is little precedent for clinical development and regulatory expectations for agents to treat MAC lung disease. As a result, we may encounter challengesdesigning this trial, including developing and reaching agreement with the FDA on the appropriate clinical endpoints. We may encounter substantial delaysin enrolling and conducting the trial, and we may not be able to enroll and conduct the trial in a manner satisfactory to the FDA or within the time periodrequired by the FDA. If the confirmatory trial is not successful or we are unable to meet the timelines required by the FDA, the FDA could, among otherthings, withdraw its approval of ARIKAYCE. Separate from the confirmatory trial, additional results from ongoing and recently completed studies may affectthe FDA’s benefit-risk analysis for the product. Additionally, ARIKAYCE is subject to post-marketing commitments consisting of implementation of ahealthcare provider communication plan, conducting a drug utilization assessment, and conducting further studies to identify an optimal quality control invitro drug release method. Failure to meet post-marketing commitments may raise additional regulatory challenges.We remain subject to substantial, ongoing regulatory requirements in the US related to ARIKAYCE, and failure to comply with these requirements couldlead to enforcement action or otherwise materially harm our business.ARIKAYCE is subject to a variety of manufacturing, packaging, storage, labeling, advertising, promotion, and record-keeping requirements,including requirements to:•Conduct sales, marketing and promotion, scientific exchange, speaker programs, charitable donations and educational grant programs in compliancewith federal and state laws;•Disclose clinical trial results and payments to health care professionals and health care organizations on publicly available databases;•Monitor and report complaints, adverse events and instances of failure to meet product specifications; and•Comply with current good manufacturing practices (cGMP) and certain quality systems requirements for device components.Failure to comply with these ongoing regulatory obligations could have significant negative consequences, including:•Issuance of warning letters or untitled letters by FDA asserting that we are in violation of the law;•Imposition of injunctions or civil monetary penalties or pursuit by regulators of civil or criminal prosecutions and fines against us or our responsibleofficers;•Suspension or withdrawal of regulatory approval;•Suspension or termination of ongoing clinical trials or refusal by regulators to approve pending marketing applications or supplements to approvedapplications;•Seizure of products, required product recalls or refusal to allow us to enter into supply contracts, including government contracts, or to import orexport products; •Suspension of, or imposition of restrictions on, our operations, including costly new manufacturing requirements with respect to ARIKAYCE; and•Negative publicity, including communications issued by regulatory authorities, which could negatively impact the perception of us or ARIKAYCEby patients, physicians, third-party payors or the health care community.We provide financial assistance with out-of-pocket costs to patients enrolled in commercial health insurance plans. In addition, independentfoundations may assist with out-of-pocket financial obligations. The ability of these organizations to provide assistance to patients is dependent on fundingfrom external sources, and we cannot guarantee that such funding will be available at adequate levels, if at all. Patient assistance programs, whether provideddirectly by manufacturers or charitable foundations, have come under recent government scrutiny. If we are deemed to fail to comply with relevant laws,regulations or government guidance with respect to these programs, we could be subject to significant fines or penalties.29Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsAny of these events could reduce market acceptance of ARIKAYCE, substantially reduce our revenue, increase the costs of operating our business,and cause us significant reputational damage, among other consequences. If we ultimately receive approval for ARIKAYCE in other jurisdictions, we expectto be subject to similar ongoing regulatory oversight by the relevant foreign regulatory authorities.If we are unable to obtain adequate reimbursement from government or third-party payors for ARIKAYCE or if we are unable to obtain acceptable pricesfor ARIKAYCE, our prospects for generating revenue and achieving profitability will be materially adversely affected.Our prospects for generating revenue and achieving profitability depend heavily upon the availability of adequate reimbursement for the use ofARIKAYCE from governmental and other third-party payors, both in the US and in other markets. We expect a substantial majority of ARIKAYCE revenuewill come from Medicare reimbursement. Reimbursement by a third-party payor depends upon a number of factors, including the third-party payor’sdetermination that use of a product is:•A covered benefit under its health plan;•Safe, effective and medically necessary;•Appropriate for the specific patient;•Cost-effective; and•Neither experimental nor investigational.ARIKAYCE's potential addition to or exclusion from the guidelines of the American Thoracic Society and Infection Diseases Society of Americamay also be a factor in this determination. Obtaining a determination of coverage and reimbursement for a product from each government or other third-partypayor is a time-consuming and costly process that could require us to provide supporting scientific, clinical and cost-effectiveness data for the use of ourproducts to each payor. We expect that, during the first six to twelve months that we commercialize ARIKAYCE, the payors will evaluate it for inclusion onformularies, during which time patients will need to rely primarily on the medical exception process to secure coverage. For sales after that time, we may notbe able to provide data sufficient to gain a positive coverage and reimbursement determination or we might need to conduct post-marketing studies in orderto demonstrate the cost-effectiveness of ARIKAYCE to such payors’ satisfaction. Such studies might require us to commit a significant amount ofmanagement time and financial and other resources.Even when a payor determines that a product is eligible for reimbursement, the payor may impose coverage limitations that preclude payment forsome uses that are approved by the FDA or non-US regulatory authorities and/or may set a reimbursement rate that is too low to support a profitable salesprice for the product. Subsequent approvals of competitive products could result in a detrimental change to the reimbursement of our products. Theoccurrence of any of these events likely would adversely impact market acceptance and demand for ARIKAYCE, which, in turn, could affect our ability tosuccessfully commercialize ARIKAYCE and adversely impact our business, financial condition, results of operations and prospects and the value of ourcommon stock.There is a significant focus in the US healthcare industry and elsewhere on drug prices and value, and public and private payors are takingincreasingly aggressive steps to control their expenditures for pharmaceuticals by, inter alia, negotiating manufacturer discounts and placing restrictions onreimbursement, and patient access to, medications. These pressures could negatively affect our business. We expect changes in the Medicare program andstate Medicaid programs, as well as managed care organizations and other third-party payors, to continue to put pressure on pharmaceutical product pricing.For instance, the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) expanded Medicare outpatient prescription drugcoverage for the elderly through Part D prescription drug plans sponsored by private entities and authorized such plans to use formularies where they canlimit the number of drugs that will be covered in any therapeutic class. The plans generally negotiate significant price concessions as a condition offormulary placement. The MMA also introduced a new reimbursement methodology based on average sales prices for physician-administered drugs, which isgenerally believed to have resulted in lower Medicare reimbursement for physician-administered drugs. These cost reduction initiatives and other provisionsof this legislation provide additional pressure to contain and reduce drug prices and could decrease the coverage and price that we receive for any approvedproducts and could seriously harm our business. Although the MMA applies only to drug benefits for Medicare beneficiaries, private payors often followMedicare coverage policy and payment limitations when setting their own reimbursement rates, and any reimbursement reduction resulting from the MMAmay result in a similar reduction in payments from private payors. Additionally, the Patient Protection and Affordable Care Act (ACA) revised the definitionof “average manufacturer price” for reporting purposes and increased the minimum percentage for Medicaid drug rebates to states, required drugmanufacturers to provide a significant discount (70% as of January 1, 2019) on prescriptions for branded drugs filled while the beneficiary is in the MedicarePart D coverage gap (also known as the donut hole), and imposed30Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentsa significant annual fee on companies that manufacture or import branded prescription drug products. We believe it is likely that the ACA, or any legislationenacted to amend or replace it, will continue the pressure on pharmaceutical pricing, especially under the Medicare program, and also may increase ourregulatory burdens and operating costs. Such changes may have a significant impact on our ability to set a product price we believe is fair and may adverselyaffect our ability to generate revenue and achieve or maintain profitability. We expect further federal and state proposals and health care reforms to continueto be proposed by legislators and/or the US President, which could limit the prices that can be charged for the products we develop or may otherwise limit ourcommercial opportunity. See Reimbursement of Pharmaceutical Products in Item 1 of Part I of this 10-K for more information. In addition, in connection withvarious government programs, we are required to report certain pricing information to the government, and the failure to do so may subject us to penalties.Payors may also restrict coverage of some products, particularly those for higher-priced drugs such as ARIKAYCE, by using a variable co-paymentstructure that imposes higher costs on patients for drugs that are not preferred by the payor and by imposing requirements for prior authorization or step edits.In markets outside the US, including countries in the European Union (EU), Japan and Canada, pricing of pharmaceutical products is subject togovernmental control. Evaluation criteria used by many EU government agencies for the purposes of pricing and reimbursement typically focus on aproduct’s degree of innovation and its ability to meet a clinical need unfulfilled by currently available therapies. The ACA created a similar entity, thePatient-Centered Outcomes Research Institute, designed to review the effectiveness of treatments and medications in federally-funded health care programs.An adverse result could lead to a treatment or product being removed from Medicare or Medicare coverage. The decisions of such governmental agenciescould affect our ability to sell our products profitably.We have had discussions with third-party payors regarding our price for ARIKAYCE, but our pricing may meet resistance from them and the publicgenerally. If we are unable to obtain adequate reimbursement of ARIKAYCE, the adoption of ARIKAYCE by physicians and patients may be limited. This, inturn, could affect our ability to successfully commercialize ARIKAYCE and adversely impact our business, financial condition, results of operations andprospects and the value of our common stock.ARIKAYCE could develop unexpected safety or efficacy concerns, which would likely have a material adverse effect on us.ARIKAYCE was granted accelerated approval from the FDA based on Month 6 data from the CONVERT study. In the US, ARIKAYCE will now beused by larger numbers of patients, potentially for longer periods of time, and we and others (including regulatory agencies and private payors) will collectextensive information on the efficacy and safety of ARIKAYCE by monitoring its use in the marketplace. In addition, we will conduct a confirmatory trial toassess and describe the clinical benefit of ARIKAYCE in patients with MAC lung disease and may conduct additional trials in connection with lifecyclemanagement programs for ARIKAYCE in the US. New safety or efficacy data from both market surveillance and our clinical trials may result in negativeconsequences including the following:•Modification to product labeling or promotional statements, such as additional boxed or other warnings or contraindications, or the issuance ofadditional “Dear Doctor Letters” or similar communications to healthcare professionals;•Required changes in the administration of ARIKAYCE;•Imposition of additional post-marketing surveillance, post-marketing clinical trial requirements, distribution restrictions or other risk managementmeasures, such as a risk evaluation and mitigation strategy (REMS) or a REMS with elements to assure safe use;•Suspension or withdrawal of regulatory approval;•Suspension or termination of ongoing clinical trials or refusal by regulators to approve pending marketing applications or supplements to approvedapplications;•Suspension of, or imposition of restrictions on, our operations, including costly new manufacturing requirements with respect to ARIKAYCE; and•Voluntary or mandatory product recalls or withdrawals from the market and costly product liability claims.Any of these circumstances could reduce ARIKAYCE’s market acceptance and would be likely to materially adversely affect our business.If estimates of the size of the potential markets for ARIKAYCE are overstated or data we have used to identify physicians is inaccurate, our ability to earnrevenue to support our business could be materially adversely affected.We have relied on our 2017 analysis of external sources, including market research funded by us and third parties, and31Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentsinternal analyses and calculations to estimate the potential market opportunities for MAC lung disease in the US, where ARIKAYCE has obtained regulatoryapproval, as well as future jurisdictions in which we may seek approval, including the EU5 (comprised of France, Germany, Italy, Spain and the UnitedKingdom) and Japan. The externally sourced information used to develop these estimates has been obtained from sources we believe to be reliable, but wehave not verified the data from such sources, and their accuracy and completeness cannot be assured. Similarly, our internal analyses and calculations arebased upon management’s understanding and assessment of numerous inputs and market conditions, including, but not limited to, the projected increase inprevalence of MAC lung disease, Medicare patient population growth and ongoing population shifts to geographies with increased rates of MAC lungdisease. These understandings and assessments necessarily require assumptions subject to significant judgment and may prove to be inaccurate. As a result,our estimates of the size of these potential markets for ARIKAYCE could prove to be overstated, perhaps materially.In addition, we are relying on third-party data to identify the physicians who treat the majority of MAC lung disease patients in the US and todetermine how to deploy our resources to market to those physicians; however, we may not be marketing to the appropriate physicians and may therefore belimiting our market opportunity.We may develop estimates with respect to market opportunities for product candidates in the future, and such estimates would be subject to similarrisks. In addition, a potential market opportunity could be reduced if a regulator limits the proposed treatment population for one of our product candidates,similar to the limited population for which ARIKAYCE was approved. In either circumstance, even if we obtain regulatory approval, we may be unable tocommercialize the product on a scale sufficient to generate significant revenue, which could have a material adverse effect on our business, financialcondition, results of operations and prospects and the value of our common stock.We currently are building our marketing and sales organization, and we have limited experience as a company in marketing drug products. If we areunable to successfully market and sell ARIKAYCE, our ability to generate revenue will be adversely affected.In order to commercialize ARIKAYCE, we must develop marketing, market access, sales and distribution capabilities on our own or makearrangements with third parties for its marketing, sale and distribution. We have commenced commercialization of ARIKAYCE in the US, but we may not besuccessful in these efforts. The establishment and development of our own sales force is and will continue to be expensive and time-consuming. As a result,we may seek one or more partners to handle some or all of the sales and marketing of ARIKAYCE in certain markets outside the US following approval by therelevant regulatory authority in those markets. However, we may not be able to enter into arrangements with third parties to sell ARIKAYCE on favorableterms or at all. In the event that either our own marketing, market access, and sales force or third-party marketing, market access, and sales organizations arenot effective, we would not be able to successfully commercialize ARIKAYCE, which would adversely affect our ability to generate revenue and materiallyharm us.ARIKAYCE was approved for treatment in a limited population of patients with refractory MAC lung disease, and additional clinical studies andregulatory applications will be required to expand its indication. We may not be successful in these trials or in obtaining such regulatory approval, whichmay materially adversely affect our prospects and the value of our common stock.The FDA granted accelerated approval of ARIKAYCE for the treatment of refractory MAC lung disease as part of a combination antibacterial drugregimen for adult patients with limited or no alternative treatment options. Our CONVERT study and 312 study focused on this refractory population, and wedo not anticipate obtaining an indication for a broader population of patients with MAC lung disease or any other illnesses or infections without additionalclinical data. Additional clinical trials will require additional time and expense. We expect to conduct our confirmatory clinical trial for full approval ofARIKAYCE in the broader population of patients with MAC lung disease, but this trial, along with any other clinical trials of ARIKAYCE may not besuccessful. Additional results from ongoing and recently completed studies may affect the FDA’s benefit-risk analysis for the product. If we are unable toexpand the indication for use of ARIKAYCE, our prospects and the value of our common stock may be materially adversely affected.Risks Related to the Development and Regulatory Approval of Our Product Candidates GenerallyPharmaceutical research and development is very costly and highly uncertain, and we may not succeed in developing product candidates in the future.Product development in the pharmaceutical industry is an expensive, high-risk, lengthy, complicated, resource intensive process. In order to developa product successfully, we must, among other things:32Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contents•Identify potential product candidates;•Submit for and receive regulatory approval to perform clinical trials;•Design and conduct appropriate preclinical and clinical trials, including confirmatory clinical trials, according to good laboratory practices andgood clinical practices and disease-specific expectations of the FDA and other regulatory bodies;•Select and recruit clinical investigators and subjects for our clinical trials;•Obtain and correctly interpret data establishing adequate safety of our product candidates and demonstrating with statistical significance that ourproduct candidates are effective for their proposed indications, as indicated by satisfaction of pre-established endpoints;•Submit for and receive regulatory approvals for marketing; and•Manufacture the product candidates and device components according to cGMP and other applicable standards and regulations.There is a high rate of failure inherent in this process, and potential products that appear promising at early stages of development may fail for anumber of reasons. Importantly, positive results from preclinical studies of a product candidate may not be predictive of similar results in human clinicaltrials, and promising results from earlier clinical trials of a product candidate may not be replicated in later clinical trials. Many companies in thepharmaceutical and biotechnology industries have suffered significant setbacks in late‑stage clinical trials even after achieving positive results in earlierstages of development and have abandoned development efforts or sought partnerships in order to continue development.In addition, there are many other difficulties and uncertainties inherent in pharmaceutical research and development that could significantly delayor otherwise materially impair our ability to develop future product candidates, including the following:•Conditions imposed by regulators, ethics committees or institutional review boards for preclinical testing and clinical trials relating to the scope ordesign of our clinical trials, including selection of endpoints and number of required patients or clinical sites;•Challenges in designing our clinical trials to support potential claims of superiority over current standard of care or future competitive therapies;•Restrictions placed upon, or other difficulties with respect to, clinical trials and clinical trial sites, including with respect to potential clinical holdsor suspension or termination of clinical trials due to, among other things, potential safety or ethical concerns or noncompliance with regulatoryrequirements;•Delayed or reduced enrollment in clinical trials, or high discontinuation rates;•Failure by third-party contractors, contract research organizations (CROs), clinical investigators, clinical laboratories, or suppliers to comply withregulatory requirements or meet their contractual obligations in a timely manner;•Greater than anticipated cost of our clinical trials; and•Insufficient product supply or inadequate product quality.Failure to successfully develop future product candidates for any of these reasons may materially adversely affect our business, financial condition,results of operations and prospects and the value of our common stock.We may not be able to obtain regulatory approvals for ARIKAYCE outside of the US or for our product candidates in the US, Europe, Japan or othermarkets. Any such failure to obtain regulatory approvals may materially adversely affect us.We are required to obtain various regulatory approvals prior to studying our products in humans and then again before we market and distribute ourproducts, and the failure to obtain such approvals will prevent us from commercializing our products, which would materially adversely affect our business,financial condition, results of operations and prospects and the value of our common stock. While we have obtained accelerated approval for ARIKAYCE inthe US, seeking approval for ARIKAYCE in other jurisdictions as well as approval for our product candidates in the US and foreign markets presentssignificant obstacles. Approval processes in the US, Europe and Japan require the submission of extensive preclinical and clinical data, manufacturing andquality information regarding the process and facility, scientific data characterizing our product and other supporting data in order to establish safety andeffectiveness. These processes are complex, lengthy, expensive, resource intensive and uncertain. Regulators will also conduct a rigorous review of any tradename we intend to use for our products. Even after they approve a trade name, these regulators may request that we adopt an alternative name for the productif adverse event reports indicate a potential for confusion with other trade names and medication error. If we are required to adopt an alternative name,potential commercialization of ARIKAYCE or our product candidates could be delayed or interrupted. We have limited experience in submitting andpursuing applications necessary to obtain these regulatory approvals.33Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsData submitted to regulators are subject to varying interpretations that could delay, limit or prevent regulatory agency approval. Even if we believeour clinical trial results are promising, regulators may disagree with our interpretation of data, study design or execution and may refuse to accept ourapplication for review or decline to grant approval. For example, in the fourth quarter of 2014, we filed a marketing authorization application (MAA) with theEuropean Medicines Agency (EMA) for ARIKAYCE as a treatment for, among other things, MAC lung disease in adult patients. The filing was based in parton data from our phase 2 study in patients with refractory MAC lung disease. We subsequently withdrew our MAA after the Committee for MedicinalProducts for Human Use concluded that the data submitted did not provide enough evidence to support an approval.In addition, the grant of a designation by the FDA or approval by the FDA does not ensure a similar decision by the regulatory authorities of othercountries, and a decision by one foreign regulatory authority does not ensure regulatory authorities in other foreign countries or the FDA will agree with thedecision. For instance, although ARIKAYCE received orphan drug designation in the US, ARIKAYCE did not qualify for orphan drug designation in Japandue to the estimated number of NTM patients in Japan exceeding 50,000. Similarly, clinical studies conducted in one country may not be accepted byregulatory authorities in other countries. Approval procedures vary among countries and can involve additional product testing, including additionalpreclinical studies or clinical trials, and administrative review periods. The time required to obtain approval in these other territories might differ from thatrequired to obtain FDA approval. We may never obtain approval for ARIKAYCE outside of the US or for our product candidates in the US or otherjurisdictions, which would limit our market opportunities and materially adversely affect our business. Even if a product candidate is approved, regulatorsmay limit the indications for which the product may be marketed, require extensive warnings on the product labeling or require expensive and time-consuming additional clinical trials or reporting as conditions of approval.We are currently assessing regulatory strategies which could expedite the development and regulatory review of INS1007 in the US and the EU, butwe may be unsuccessful in pursuing such strategies. The FDA has denied our request for orphan drug designation for INS1007 in on-cystic fibrosis (non-CF)bronchiectasis. In addition, although we believe that INS1009 could be eligible for approval under Section 505(b)(2), and thus could rely at least in part onstudies not conducted by or for us and for which we do not have a right of reference, we may not obtain approval from the FDA to use this pathway.We may also encounter delays or rejections based on changes in regulatory agency policies during the period in which we develop a product and theperiod required for review of any application for regulatory agency approval of a particular product. Resolving such delays could force us or third parties toincur significant costs, limit our allowed activities or the allowed activities of third parties, diminish any competitive advantages that we or our third partiesmay attain or adversely affect our ability to receive royalties, any of which could materially adversely affect our business, financial condition, results ofoperations and prospects and the value of our common stock.For ARIKAYCE to be commercialized in a given market, in addition to regulatory approvals required for ARIKAYCE, the Lamira Nebulizer System mustsatisfy certain regulatory requirements and its use as a delivery system for ARIKAYCE must be approved or cleared by regulators.ARIKAYCE is administered using the Lamira Nebulizer System, and the Lamira Nebulizer System must receive regulatory approval or clearance onits own or in conjunction with ARIKAYCE as a combination product in order for us to develop and commercialize ARIKAYCE in a given market. The FDAgranted accelerated approval of the Lamira Nebulizer System with ARIKAYCE as part of the approval of the drug/device combination product, and theLamira Nebulizer System is CE marked by PARI in the EU. However, outside the US and EU, the Lamira Nebulizer System is labeled as investigational foruse in our clinical trials, including in Japan, Canada and Australia, and is not approved for commercial use in Japan, Canada or certain other markets in whichwe may seek to commercialize ARIKAYCE in the future.If we seek regulatory approval in markets in which the Lamira Nebulizer System is not approved and we and PARI are not successful in obtainingapproval for the Lamira Nebulizer System, our ability to commercialize ARIKAYCE in those markets would be materially impaired. In addition, failure tomaintain regulatory approval or clearance of the Lamira Nebulizer System could result in increased development costs, withdrawal of regulatory approval,and delays in ARIKAYCE reaching the market. Failure to obtain or maintain regulatory approval or clearance of the Lamira Nebulizer System could result inpotential loss of regulatory approval or otherwise materially harm our business.We have limited experience conducting and managing the preclinical development activities and clinical trials necessary to obtain regulatory approvals,and we may not succeed in doing so in the future.ARIKAYCE is our first approved product candidate since our merger with Transave, and we have limited experience in conducting and managingthe preclinical development activities and clinical trials necessary to obtain regulatory approvals,34Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentsincluding approval by the FDA, EMA, Ministry of Health, Labour and Welfare (MHLW), and Pharmaceuticals and Medical Devices Agency (PMDA), whichmight prevent us from successfully designing, implementing, or completing the clinical trials required to support regulatory approval of our productcandidates. The application processes for the FDA, MHLW, PMDA, EMA and other regulatory agencies are complex and difficult and vary by regulatoryagency, and we might not be able to demonstrate that our product candidates meet the appropriate standards for regulatory approval or commercialize ourproduct candidates in the US or elsewhere, or commercialize ARIKAYCE in jurisdictions outside of the US, or we might be significantly delayed in doing so.In such circumstances, our business, financial condition, results of operations and prospects and the value of our common stock may be materially adverselyaffected.If our clinical studies do not produce positive results or our clinical trials are delayed, or if serious side effects are identified during drug development, wemay experience delays, incur additional costs and ultimately be unable to commercialize our product candidates in the US, Europe, Japan or othermarkets.Before obtaining regulatory approval for the sale of our product candidates, we must conduct, at our own expense, extensive preclinical tests todemonstrate the safety of our product candidates in animals, and clinical trials to demonstrate the safety and efficacy of our product candidates in humans. Ifwe experience delays in our clinical trials or other testing or the results of these trials or tests are not positive or are only modestly positive, including withrespect to safety, we may:•Experience increased product development costs;•Be delayed in obtaining, or be unable to obtain, regulatory approval for one or more of our product candidates;•Obtain approval for indications or patient populations that are not as broad as intended or entirely different than those indications for which wesought approval or with labeling with boxed warnings or other warnings or contraindications;•Need to change the way the product is administered;•Be required to perform additional clinical trials to support approval or be subject to additional post-marketing testing requirements;•Have regulatory authorities withdraw, or suspend, their approval of the product or impose risk mitigation strategies such as restrictions ondistribution or other REMS;•Face a shortened patent protection period during which we may have the exclusive right to commercialize our products;•Have competitors that are able to bring similar products to market before us;•Be sued for alleged injuries caused to patients using our products; or•Suffer reputational damage.Such circumstances would impair our ability to commercialize our products and harm our business and results of operations.We may not be able to enroll enough patients to conduct and complete our clinical trials or retain a sufficient number of patients in our clinical trials togenerate the data necessary for regulatory approval of our product candidates.The completion rate of our clinical trials is dependent on, among other factors, the patient enrollment rate. Patient enrollment is a function of manyfactors, including:•Investigator identification and recruitment;•Regulatory approvals to initiate study sites;•Patient population size;•The nature of the protocol to be used in the trial;•Patient proximity to clinical sites;•Eligibility criteria for the trial;•Patient willingness to participate in the trial;•Discontinuation rates; and•Competition from other companies’ potential clinical trials for the same patient population.Delays in patient enrollment for our clinical trials, including in the confirmatory clinical trial for ARIKAYCE and the WILLOW study, our globalphase 2 study of INS1007 in non-CF bronchiectasis that currently is enrolling patients, like those we encountered in enrolling the CONVERT study, couldincrease costs and delay commercialization and sales, if any, of our products. Once enrolled, patients may elect to discontinue participation in a clinical trialat any time. If patients elect to discontinue participation in our clinical trials at a higher rate than expected, we may be unable to generate the data requiredby regulators for approval of our product candidates.35Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsRisks Related to Our Reliance on Third PartiesWe rely on third parties including collaborators, CROs, clinical and analytical laboratories, contract manufacturing organizations (CMOs) and otherproviders for many services that are critical to our business. If we are unable to form and sustain these relationships, or if any third-party arrangementsthat we may enter into are unsuccessful, including due to non-compliance by such third parties with our agreements or applicable law, our ability todevelop and commercialize our products may be materially adversely affected.We currently rely, and expect to continue to rely, on third parties for significant research, analytical services, preclinical development, clinicaldevelopment and manufacturing of our product candidates and commercial scale manufacturing of ARIKAYCE and the Lamira Nebulizer System. Forexample, we do not own facilities for clinical-scale or commercial manufacturing of our product candidates, and we currently rely on Therapure BiopharmaInc. (Therapure) and Ajinimoto Althea, Inc. (Althea) to provide our clinical and commercial supply of ARIKAYCE. Additionally, almost all of our clinicaltrial work is done by CROs, such as SynteractHCR, Inc., our CRO for both the CONVERT and 312 studies, and clinical laboratories. Reliance on these thirdparties poses a number of risks, including the following:•The diversion of management time and cost of third-party advisers associated with the negotiation, documentation and implementation ofagreements with third parties in the pharmaceutical industry;•The inability to control whether third parties devote sufficient resources to our programs or products, including with respect to meeting contractualdeadlines;•The inability to control the regulatory and contractual compliance of third parties, including their quality systems, processes and procedures,systems utilized to collect and analyze data, and equipment used to test drug product and/or clinical supplies;•The inability to establish and implement collaborations or other alternative arrangements on favorable terms;•Disputes with third parties, including CROs, leading to loss of intellectual property rights, delay or termination of research, development, orcommercialization of product candidates or litigation or arbitration;•Contracts with our collaborators fail to provide sufficient protection of our intellectual property; and•Difficulty enforcing our contractual rights if one of these third parties fails to perform.We also rely on third parties to select and enter into agreements with clinical investigators to conduct clinical trials to support approval of ourproduct candidates, and the failure of these third parties to appropriately carry out such evaluation and selection can adversely affect the quality of the datafrom these studies and, potentially, the approval of our products. In particular, as part of future drug approval submissions to the FDA, we must disclosecertain financial interests of investigators who participated in any of the clinical studies being submitted in support of approval, or must certify to theabsence of such financial interests. The FDA evaluates the information contained in such disclosures to determine whether disclosed interests may have animpact on the reliability of a study. If the FDA determines that financial interests of any clinical investigator raise serious questions of data integrity, the FDAcan institute a data audit, request that we submit further data analyses, conduct additional independent studies to confirm the results of the questioned study,or refuse to use the data from the questioned study as a basis for approval. A finding by the FDA that a financial relationship of an investigator raises seriousquestions of data integrity could delay or otherwise adversely affect approval of our products.These risks could materially harm our business, financial condition, results of operations and prospects and the value of our common stock.We may not have, or may be unable to obtain, sufficient quantities of ARIKAYCE, the Lamira Nebulizer System or our product candidates to meet ourrequired supply for commercialization or clinical studies, which would materially harm our business.We do not have any in-house manufacturing capability other than for small-scale pre-clinical development programs and depend completely on asmall number of third-party manufacturers and suppliers for the manufacture of our product candidates on a clinical or commercial scale. For instance, we areand expect to remain dependent upon Therapure, Althea and eventually Patheon to supply ARIKAYCE both for our clinical trials and commercial sale.Althea manufactures ARIKAYCE at a relatively small scale; Therapure, operates at a larger scale than Althea. ARIKAYCE currently has a limited shelf life,and we may not be able to maintain adequate quantities to meet future demand. As additional supporting data become available, we believe the currentapproved shelf life for product manufactured at our CMOs will increase. If we encounter delays or difficulties in the manufacturing process that disrupt ourability to supply our distributors with ARIKAYCE, we may experience a product stock-out, which would likely have a material adverse effect on our businessand reputation. In addition, we have entered into certain agreements with Patheon related to increasing our long-term production capacity for ARIKAYCEcommercial inventory, although Patheon’s supply obligations will commence only after certain technology transfer and36Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentsconstruction services are completed. Any delay in the commencement of Patheon’s supply obligations, whether due to delays in technology transfer andconstruction or from adding Patheon to our NDA as a CMO, would increase the risks associated with either Therapure or Althea being unable to provide uswith an adequate supply of ARIKAYCE.We are also dependent upon PARI being able to provide an adequate supply of nebulizers both for commercial sale of ARIKAYCE and any ongoingclinical trials, as PARI is the sole manufacturer of the Lamira Nebulizer System. We have no alternative supplier for the nebulizer, and because significanteffort and time were expended in the optimization of the nebulizer for use with ARIKAYCE, we do not intend to seek an alternative or secondary supplier. Inthe event PARI cannot provide us with sufficient quantities of the nebulizer, replication of the optimized device by another party would likely requireconsiderable time and additional regulatory approval. In the case of certain specified supply failures, we have the right under our commercializationagreement with PARI to make the nebulizer and have it made by certain third parties, but not those deemed under the commercialization agreement tocompete with PARI.We do not have long-term commercial agreements with all of our suppliers and if any of our suppliers are unable or unwilling to perform for anyreason, we may not be able to locate suppliers or enter into favorable agreements with them.An inadequate supply of ARIKAYCE or the Lamira Nebulizer System could harm our commercial efforts or delay or impair clinical trials ofARIKAYCE or our product candidates and adversely affect our business, financial condition, results of operations and prospects and the value of ourcommon stock.The manufacturing facilities of our third-party manufacturers are subject to significant government regulations and approvals, which are often costly andcould result in adverse consequences to our business if we and our manufacturing partners fail to comply with the regulations or maintain the approvals.Manufacturers of ARIKAYCE, the Lamira Nebulizer System and our product candidates are subject to cGMP, Quality System Regulations andsimilar standards. While we have policies and procedures in place to select third-party manufacturers for our product and product candidates that adhere, andmonitor their adherence to, such standards, they may nonetheless fail to do so. Similarly, while we have entered into a Commercialization Agreement withPARI for the manufacture of the Lamira Nebulizer System for use with ARIKAYCE, PARI may fail to adhere to applicable standards. These manufacturers andtheir facilities will be subject to periodic review and inspections by the FDA and other regulatory authorities following regulatory approval of our products,as with ARIKAYCE. For instance, to monitor compliance with applicable regulations, the FDA routinely conducts inspections of facilities and may identifypotential deficiencies. The FDA issues what are referred to as “FDA Form 483s” that set forth observations and concerns identified during its inspections.Failure to satisfactorily address the concerns or potential deficiencies identified in a Form 483 could result in the issuance of a warning letter, which is anotice of the issues that the FDA believes to be significant regulatory violations requiring prompt corrective actions. Failure to respond adequately to awarning letter, or to otherwise fail to comply with applicable regulatory requirements could result in enforcement, remedial and/or punitive actions by theFDA or other regulatory authorities.If one of these manufacturers fails to maintain compliance with regulatory requirements or experiences supply problems, including in the scale-up ofcommercial production, the production of ARIKAYCE, the Lamira Nebulizer System and our product candidates could be interrupted, resulting in delays,additional costs or restrictions on the marketing or sale of our products. An alternative manufacturer would need to be qualified, through regulatory filings,which could result in further delay. The regulatory authorities may also require additional testing if a new manufacturer is relied upon for commercialproduction. In addition, with respect to our product candidates, our manufacturers and their facilities are subject to pre-approval cGMP inspection by theFDA and other regulatory authorities, and the findings of the cGMP inspection could result in a failure to obtain, or a delay in obtaining, regulatory approvalfor future product candidates.Risks Related to the Operation of our BusinessWe are dependent upon retaining and attracting key personnel, the loss of whose services could materially adversely affect our business, financialcondition, results of operations and prospects and the value of our common stock.We depend heavily on our management team and our principal clinical and commercial personnel, the loss of whose services might significantlydelay or prevent the achievement of our research, development or commercialization objectives. Our success depends, in large part, on our ability to attractand retain qualified management, clinical and commercial personnel, and on our ability to develop and maintain important relationships with commercialpartners, leading research institutions and key distributors.Competition for skilled personnel in our industry and market is intense because of the numerous pharmaceutical and37Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentsbiotechnology companies that seek similar personnel. These companies may have greater financial and other resources, offer a greater opportunity for careeradvancement and have a longer history in the industry than we do. We also experience competition for the hiring of our clinical and commercial personnelfrom universities, research institutions, and other third parties. We cannot assure that we will attract and retain such persons or maintain such relationships.Our inability to retain and attract qualified employees would materially harm our business, financial condition, results of operations and prospects and thevalue of our common stock.We expect to expand our development, regulatory and sales and marketing capabilities, and as a result, we may encounter difficulties in managing ourgrowth, which could disrupt our operations.In connection with our commercial launch of ARIKAYCE and international expansion, we expect to experience significant growth in the number ofour employees and the scope of our operations, particularly in the areas of drug development, regulatory affairs, quality, commercial compliance, medicalaffairs, and sales and marketing. For example, we plan to hire additional personnel in connection with our commercial launch of ARIKAYCE and preparationfor potential regulatory filings for ARIKAYCE in other markets. To manage our anticipated future growth, we must continue to implement and improve ourmanagerial, operational and financial systems, expand our facilities and continue to recruit and train additional qualified personnel. Due to the limitedexperience of our management team in managing a company with this anticipated growth, we may not be able to effectively manage the expansion of ouroperations or recruit and train additional qualified personnel. The physical expansion of our operations may lead to significant costs and may divert ourmanagement and business development resources. We may not be able to effectively manage the expansion of our operations, which could delay theexecution of our business plans or disrupt our operations.Any acquisitions we make, or collaborative relationships we enter into, may not be clinically or commercially successful, and may require financing or asignificant amount of our available cash, which could adversely affect our business.As part of our business strategy, we may effect acquisitions to obtain additional businesses, products, technologies, capabilities and personnel.Acquisitions involve a number of operational risks, including:•Failure to achieve expected synergies;•Difficulty and expense of assimilating the operations, technology and personnel of any acquired business;•The inability to retain the management, key personnel and other employees of any acquired business;•The inability to maintain any acquired company’s relationship with key third parties, such as alliance partners;•Exposure to legal claims for activities of any acquired business prior to acquisition;•Diversion of our management’s attention from our core business; and•Potential impairment of intangible assets, adversely affecting our reported results of operations and financial condition.We also may enter into collaborative relationships that would involve our collaborators conducting proprietary development programs.Disagreements with collaborators may develop over the rights to our intellectual property, and any conflict with our collaborators could limit our ability toobtain future collaboration agreements and negatively influence our relationship with existing collaborators.If we make one or more significant acquisitions or enter into a significant collaboration in which the consideration includes cash, we may berequired to use a substantial portion of our available cash and/or need to raise additional capital, which could adversely affect our financial condition.We may be subject to product liability claims, and we have only limited product liability insurance.The manufacture and sale of human therapeutic products involve an inherent risk of product liability claims, particularly as we now commercializeARIKAYCE in the US. Regardless of merit or eventual outcome, liability claims may result in:•decreased demand for ARIKAYCE and any other products that we may commercialize, and a corresponding loss of revenue;•substantial monetary awards to patients or trial participants;•significant time and costs to defend the related litigation;•withdrawal or reduced enrollment of clinical trial participants; and•reputational harm and significant negative media attention.38Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsWe currently have only limited product liability insurance for our products. We do not know if we will be able to maintain existing, or obtainadditional, product liability insurance on acceptable terms or with adequate coverage against potential liabilities. This type of insurance is expensive andmay not be available on acceptable terms. If we are unable to obtain or maintain sufficient insurance coverage on reasonable terms or to otherwise protectagainst potential product liability claims, we may be unable to commercialize our products. A successful product liability claim brought against us in excessof our insurance coverage, if any, may require us to pay substantial amounts and may materially adversely affect our business, financial condition, results ofoperations and prospects and the value of our common stock.Our business and operations, including our drug development programs, could be materially disrupted in the event of system failures, security breaches,violations of data protection laws or data loss or damage by us or our CROs or other contractors or consultants. Despite the implementation of security measures, our internal computer systems and those of our CROs and other contractors and consultants arevulnerable to damage from computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures. If such anevent were to occur and cause interruptions in our operations, it could have a material adverse effect on our business operations, including a materialdisruption of our drug development and commercialization programs. Unauthorized disclosure of sensitive or confidential patient or employee data,including personally identifiable information, whether through breach of computer systems, systems failure, employee negligence, fraud or misappropriation,or otherwise, or unauthorized access to or through our information systems and networks, whether by our employees or third parties, could result in negativepublicity, legal liability and damage to our reputation. Unauthorized disclosure of personally identifiable information could also expose us to sanctions forviolations of data privacy laws and regulations around the world. To the extent that any disruption or security breach resulted in a loss of or damage to ourdata or applications, or inappropriate disclosure of confidential or proprietary information, we could incur liability and the further development of ourproduct candidates could be delayed. For example, the loss of or damage to clinical trial data, such as from completed or ongoing clinical trials, for any of ourproduct candidates could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. Although we have general liability insurance coverage, including coverage for errors and omissions, our insurance may not cover all claims,continue to be available on reasonable terms or be sufficient in amount to cover one or more large claims; additionally, the insurer may disclaim coverage asto any claim. The successful assertion of one or more large claims against us that exceed or are not covered by our insurance coverage or changes in ourinsurance policies, including premium increases or the imposition of large deductible or co-insurance requirements, could have a material adverse effect onour business, financial condition, results of operations and prospects and the value of our common stock.We have limited experience operating internationally, are subject to a number of risks associated with our international activities and operations and maynot be successful in our efforts to expand internationally.We currently have limited operations outside of the US. As of December 31, 2018, we had 28 employees located in Europe and 6 employees locatedin Japan, although we have clinical trial sites and suppliers located around the world. In order to meet our long-term goals, we expect to grow ourinternational operations over the next several years, including in Europe and Japan, and continue to source material used in the manufacture of our productcandidates from abroad. Consequently, we are and will continue to be subject to risks related to operating in foreign countries, including:•Limited experience with international regulatory requirements;•An inability to achieve optimal pricing and reimbursement for ARIKAYCE, if approved in another jurisdiction, or subsequent changes inreimbursement, pricing and other regulatory requirements;•Any implementation of, or changes to, tariffs, trade barriers and other import-export regulations in the US or other countries in which we, or ourthird-party partners, operate;•Unexpected adverse events related to ARIKAYCE or our product candidates occurring in foreign markets that we have not experienced in the US;•Economic and political conditions, including geopolitical events, such as war and terrorism, foreign currency fluctuations and inflation, whichcould result in reduced revenue, increased or unpredictable operating expenses and other obligations incident to doing business in, or with acompany located in, another country;•Changes resulting from the UK's vote to exit the EU, including: (i) the uncertainty and instability in economic and market conditions; (ii) theuncertainty regarding the UK’s access to the EU Single Market and the impact on the wider trading, legal, regulatory and labor environments; and(iii) the uncertainty in the European regulatory framework, including the relocation of the EMA from the UK to the Netherlands, and the subsequentpotential disruption and delay of EMA regulatory actions; and•Compliance with foreign or US laws, rules and regulations, including data privacy requirements, labor relations laws,39Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentstax laws, anti-competition regulations, import, export and trade restrictions, anti-bribery/anti-corruption laws, regulations or rules, which could leadto actions by us or our licensees, distributors, manufacturers, other third parties who act on our behalf or with whom we do business in foreigncountries or our employees who are working abroad that could subject us to investigation or prosecution under such foreign or US laws.These and other risks associated with our international operations may materially adversely affect our business, financial condition, results ofoperations and prospects and the value of our common stock.We operate in a highly competitive and changing environment, and if we are unable to adapt to our environment, we may be unable to competesuccessfully.Biotechnology and related pharmaceutical technology have undergone and are likely to continue to experience rapid and significant change. Ourfuture success will depend in large part on our ability to maintain a competitive position with respect to these technologies and to obtain and maintainprotection for our intellectual property. Compounds, products or processes that we develop may become obsolete before we recover any expenses incurred inconnection with their development. We face substantial competition from pharmaceutical, biotechnology and other companies, universities and researchinstitutions with respect to nontuberculous mycobacteria (NTM) lung disease, bronchiectasis, and pulmonary arterial hypertension (PAH). Relative to us,most of these entities have substantially greater capital resources, research and development staffs, facilities and experience in conducting clinical studies,obtaining regulatory approvals, and manufacturing and marketing pharmaceutical products. Many of our competitors may achieve productcommercialization or obtain patent protection earlier than us. Furthermore, we believe that our competitors have used, and may continue to use, litigation togain a competitive advantage. Our competitors may also use different technologies or approaches to develop products similar to ARIKAYCE and our productcandidates.We expect that competing successfully will depend, among other things, on the relative speed with which we can develop products, complete theclinical testing and regulatory approval processes and supply commercial quantities of the product to the market, as well as product efficacy, safety,reliability, availability, timing and scope of regulatory approval and price. We expect competition to increase as technological advances are made andcommercial applications broaden. There are potential competitive products, both approved and in development, which include oral, systemic, or inhaledantibiotic products to treat chronic respiratory infections. For instance, certain entities have expressed interest in studying their products for NTM lungdisease and are seeking to advance studies in NTM lung disease caused by mycobacterial species other than MAC; however, we are not aware of any entitiescurrently conducting clinical trials for the treatment of refractory MAC lung disease or of any other approved inhaled therapies specifically indicated forNTM lung disease in North America, Europe or Japan. If any of our competitors develops a product that is more effective, safe, tolerable or, convenient or lessexpensive than ARIKAYCE or our product candidates, it would likely materially adversely affect our ability to generate revenue. We also may face lowerpriced generic competitors if third-party payors encourage use of generic or lower-priced versions of our product or if competing products are imported intothe US or other countries where we may sell ARIKAYCE. In addition, in an effort to put downward pressure on drug pricing, Congress and the FDA areworking to facilitate generic competition, which could result in our experiencing competition earlier than otherwise would be the case.There are also other amikacin products that have been approved by the FDA, MHLW and other regulatory agencies for use in other indications, andphysicians may elect to prescribe those products rather than ARIKAYCE to treat the indications for which ARIKAYCE has received approval, which iscommonly referred to as off-label use. Although regulations prohibit a drug company from promoting off-label use of its product, the FDA and otherregulatory agencies do not regulate the practice of medicine and cannot direct physicians as to what product to prescribe to their patients. As a result, wewould have limited ability to prevent any off-label use of a competitor’s product to treat diseases for which we have received FDA or other regulatory agencyapproval, even if this use violates our patents or any statutory exclusivities that the FDA may grant for the use of amikacin to treat such diseases. If we areunable to compete successfully, it will materially adversely affect our business, financial condition, results of operations and prospects and the value of ourcommon stock.Risks Related to Our Intellectual PropertyIf we are unable to protect our intellectual property rights adequately, the value of ARIKAYCE and our product candidates could be materiallydiminished.The patent position of biotechnology and pharmaceutical companies generally is highly uncertain and involves complex legal, technical, scientificand factual questions, and our success depends in large part on our ability to protect our proprietary technology and to obtain and maintain patent protectionfor our products, prevent third parties from infringing our patents, both domestically and internationally. We have sought to protect our proprietary positionby filing patent applications in the US and abroad related to our novel technologies and products that are important to our business. This process isexpensive and time-consuming, and we may not be able to file and prosecute all necessary or desirable patent applications at a40Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentsreasonable cost or in a timely manner. It is also possible that we will fail to identify patentable aspects of our research and development output before it is toolate to obtain patent protection. Our existing patents and any future patents we obtain may not be sufficiently broad to prevent others from using ourtechnologies or from developing competing products and technologies.Even if our owned and licensed patent applications issue as patents, they may not issue in a form that will provide us with any meaningfulprotection or otherwise provide us with any competitive advantage. Any conclusions we may reach regarding non-infringement, inapplicability or invalidityof a third-party’s intellectual property vis-à-vis our proprietary rights, or those of a licensor, are based in significant part on a review of publicly availabledatabases and other information. There may be information not available to us or otherwise not reviewed by us that could render these conclusionsinaccurate. Our competitors may also be able to circumvent our owned or licensed patents by developing similar or alternative technologies or products in anon-infringing manner.Additionally, patents issued to us or our licensors may be challenged, narrowed, invalidated, held to be unenforceable or circumvented throughlitigation, which could limit our ability to stop competitors from marketing similar products or reduce the term of patent protection for amikacin liposomeinhalation suspension or our product candidates. US patents and patent applications may also be subject to interference or derivation proceedings, and USpatents may be subject to re-examination proceedings, reissue, post-grant review and/or inter partes review in the USPTO. Our foreign patents have been andmay be in the future subject to opposition or comparable proceedings in the corresponding foreign patent office, which could result in either loss of thepatent or denial of the patent application or loss or reduction in the scope of one or more of the claims of the patent or patent application. See IntellectualProperty - ARIKAYCE Patents and Trade Secrets in Item 1 of Part I of this 10-K for more information on our European patents that have been previouslyopposed.Changes in either patent laws or in interpretations of patent laws in the US and other countries may also diminish the value of our intellectualproperty or narrow the scope of our patent protection, including making it easier for competitors to challenge our patents. For example, the America InventsAct included a number of changes to established practices, including the transition to a first-inventor-to-file system and new procedures for challengingpatents and implementation of different methods for invalidating patents.If we are not able to adequately prevent disclosure of trade secrets and other proprietary information, the value of ARIKAYCE and our product candidatescould be materially diminished.We rely on trade secrets to protect our proprietary technologies, especially where we do not believe patent protection is appropriate or obtainable.However, trade secrets are difficult to protect. We rely in part on confidentiality agreements with our employees, consultants, advisors, collaborators, andother third parties and partners to protect our trade secrets and other proprietary information. These agreements may not effectively prevent disclosure ofconfidential information or may not provide an adequate remedy in the event of unauthorized disclosure of confidential information. In addition, thirdparties may independently develop or discover our trade secrets and proprietary information. Regulators also may disclose information we consider to beproprietary to third parties under certain circumstances, including in response to third-party requests for such disclosure under the Freedom of InformationAct or comparable laws. Additionally, the FDA, as part of its Transparency Initiative, continues to consider whether to make additional information publiclyavailable on a routine basis, including information that we may consider to be trade secrets or other proprietary information, and it is not clear at the presenttime whether and how the FDA’s disclosure policies may change in the future.We may not be able to enforce our intellectual property rights throughout the world, which could harm our business.The legal systems of some foreign countries, particularly developing countries, do not favor the enforcement of patents and other intellectualproperty protection, especially those relating to life sciences. Many companies have encountered significant problems in protecting and defendingintellectual property rights in such foreign jurisdictions. For example, certain foreign countries have compulsory licensing laws under which a patent ownermay be required to grant licenses to third parties. In addition, many countries limit the enforceability of patents against third parties, including governmentagencies or government contractors. In these countries, patents may provide limited or no benefit. This legal environment could make it difficult for us tostop the infringement of our patents or in-licensed patents or the misappropriation of our other intellectual property rights. Proceedings to enforce our patentrights in foreign jurisdictions could result in substantial costs and divert our efforts and attention from other aspects of our business, and our efforts to protectour intellectual property rights in such countries may be inadequate.The drug research and development industry has a history of intellectual property litigation, and we could become involved in costly intellectual propertydisputes, which could delay or impair our product development efforts or prevent us from, or41Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentsincrease the cost of, commercializing ARIKAYCE or any other approved product candidate.Third parties may claim that we have infringed upon or misappropriated their proprietary rights. Any existing third-party patents, or patents that maylater issue to third parties, could negatively affect our commercialization of ARIKAYCE, INS1007, INS1009 or any other product candidate that receivesregulatory approval. For instance, PAH is a competitive indication with established products, including other formulations of treprostinil. Our supply of theactive pharmaceutical ingredient for INS1009 is dependent upon a single supplier. The supplier owns patents on its manufacturing process, and we have filedpatent applications for INS1009; however, a competitor in the PAH indication may claim that we or our supplier have infringed upon or misappropriated itsproprietary rights. Moreover, in the event that we pursue approval of INS1009, or any other product candidate, via the 505(b)(2) regulatory pathway, we willbe required to file a certification against any unexpired patents listed in the Orange Book for the third-party drug we rely upon as part of our regulatorysubmission. This certification process may lead to litigation and could also delay launch of a product candidate, if approved by regulators.In the event of successful litigation or settlement of claims against us for infringement or misappropriation of a third-party’s proprietary rights, as in2007 with respect to IPLEX, we may be required to take actions including but not limited to the following:•Paying damages, including up to treble damages, royalties, and the other party’s attorneys’ fees, which may be substantial;•Ceasing development, manufacture, marketing and sale of products or use of processes that infringe the proprietary rights of others;•Expending significant resources to redesign our products or our processes so that they do not infringe the proprietary rights of others, which may notbe possible, or may result in significant regulatory delays associated with conducting additional clinical trials or other steps to obtain regulatoryapproval; and/or•Acquiring one or more licenses from third parties, which may not be available to us on acceptable terms or at all.We may also have to undertake costly litigation or engage in other proceedings, such as interference or inter partes review, to enforce or defend thevalidity of any patents issued or licensed to us, to confirm the scope and validity of our or a licensor’s proprietary rights or to defend against allegations thatwe have infringed a third-party’s intellectual property rights.Any proceedings regarding our intellectual property rights are likely to be time consuming and may divert management attention from operation of ourbusiness, and could have a material adverse effect on our business, financial condition, results of operations and prospects and the value of our commonstock.Certain of the agreements to which we are, or may become, a party relating to ARIKAYCE and our product candidates impose, or may in the futureimpose, restrictions on our business or other material obligations on us. If we fail to comply with these obligations, our business could be adverselyaffected, including as a result of the loss of license rights that are important to our business.We are a party to various agreements related to ARIKAYCE and our product candidates, including licensing agreements with PARI and AstraZeneca,which we view as material to our business. For additional information regarding the terms of these agreements, see Business - License and Other Agreementsin Item 1 of Part I of this 10-K. These agreements impose a number of obligations on us and our business, including restrictions on our ability to freelydevelop or commercialize our product candidates and requirements to make milestone and royalty agreements to our counterparties upon certain events.Under our license agreement with AstraZeneca, AstraZeneca retains a right of first negotiation pursuant to which it may exclusively negotiate with us beforewe can negotiate with a third-party regarding any transaction to develop or commercialize INS1007, subject to certain exceptions. While this right of firstnegotiation is not triggered by a change of control, it may impede or delay our ability to consummate certain other transactions involving INS1007.If we fail to comply with our obligations under these agreements, our counterparties may have the right to take action against us, up to and includingtermination of a relevant license. For instance, under our licensing agreement with PARI, with respect to NTM lung disease and bronchiectasis, we havespecific obligations to use commercially reasonable efforts to achieve certain developmental and regulatory milestones by set deadlines. Additionally, forNTM lung disease, we are obligated to use commercially reasonable efforts to achieve certain commercial milestones in Europe. The consequences of ourfailing to use commercially reasonable efforts to achieve certain commercial milestones are context-specific, but include ending PARI’s non-competeobligation, making the license non-exclusive and terminating the license, in each case with respect to the applicable indication. Similarly, under our licenseagreement with AstraZeneca, AstraZeneca may terminate our license to INS1007 if we fail to use commercially reasonable efforts to develop andcommercialize a product based on INS1007, or we are subject to a bankruptcy or insolvency. Reduction or elimination of our licensed rights may result in ourhaving to negotiate new or reinstated licenses with less favorable terms and may materially harm our business.42Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsFinally, if we do not proceed with the development of our ARIKAYCE program in the NTM lung disease or CF indications, certain of our contractcounterparties may elect to proceed with the development of these indications.Risks Related to Government RegulationGovernment health care reform could materially increase our costs, which could materially adversely affect our business, financial condition, results ofoperations and prospects and the value of our common stock.Our industry is highly regulated and changes in or revisions to laws and regulations that make gaining regulatory approval, reimbursement andpricing more difficult or subject to different criteria and standards may adversely impact our business, operations or financial results.The Administration and the majority party in the Senate have indicated their ongoing desire to repeal the ACA and, in December 2017, Congressrepealed the ACA's individual mandate, i.e., the penalty imposed on individuals who do not obtain health care coverage. It is unclear what the effect of thispartial repeal will be and whether, when and how repeal of other sections of the law may be effectuated and what the effect on the healthcare sector will be. InDecember 2018, a federal district court judge in Texas found the ACA to be unconstitutional, although the ruling was stayed while the case is appealed. It isunclear what the outcome of this litigation and other pending challenges to the ACA's constitutionality, as well as the effect of these matters on thehealthcare sector, will be. The US President has indicated an interest in taking steps to lower drug prices, such as having the federal government negotiatedrug prices with pharmaceutical manufacturers and/or in indexing certain federally reimbursement payments to international drug prices. See Reimbursementof Pharmaceutical Products in Item 1 of Part I of this 10-K for more information. Changes to the ACA, to the Medicare or Medicaid programs, or to theability of the federal government to negotiate or otherwise affect drug prices, or other federal legislation regarding healthcare access, financing or legislationin individual states, could affect our business, financial condition, results of operations and prospects and the value of our common stock. It remains unclearhow any new legislation or regulation might affect the prices we may obtain for ARIKAYCE or any of our product candidates for which regulatory approvalis obtained.If we are found in violation of federal or state “fraud and abuse” laws, we may be required to pay a penalty or may be suspended from participation infederal or state health care programs, which may adversely affect our business, financial condition, results of operations and prospects and the value ofour common stock.In the US, we are subject to various federal and state health care “fraud and abuse” laws, including anti‑kickback laws, false claims laws and otherlaws intended to reduce fraud and abuse in federal and state health care programs. Although we seek to structure our business arrangements in compliancewith all applicable requirements, these laws are broadly written, and it is often difficult to determine precisely how the law will be applied in specificcircumstances. Accordingly, it is possible that our practices may be challenged under these laws. Violations of fraud and abuse laws may be punishable bycriminal and/or civil sanctions, including fines or exclusion or suspension from federal and state health care programs such as Medicare and Medicaid anddebarment from contracting with the US government, and our business, financial condition, results of operations and prospects and the value of our commonstock may be adversely affected. Our reputation could also suffer. In addition, private individuals have the ability to bring actions on behalf of thegovernment under the federal False Claims Act as well as under the false claims laws of several states.Under the ACA, we are required to report information on payments or transfers of value to US physicians and teaching hospitals as well asinvestment interests held by physicians and their immediate family members, which is posted in searchable form on a public website. Failure to submitrequired information may result in civil monetary penalties.Several states also impose other marketing restrictions or require pharmaceutical companies to make marketing or price disclosures to the state. Inaddition to the federal government, some states, as well as other countries, including France, require the disclosure of certain payments to health careprofessionals. The federal privacy regulations under HIPAA, state, and foreign medical record privacy laws may limit access to information identifying thoseindividuals who may be prospective users. There are ambiguities as to what is required to comply with these state requirements, and we could be subject topenalties if a state determines that we have failed to comply with an applicable state law requirement.We are subject to anti-corruption laws and trade control laws, as well as other laws governing our operations. If we fail to comply with these laws, wecould be subject to negative publicity, civil or criminal penalties, other remedial measures, and legal expenses, which could adversely affect our business,financial condition, results of operations and prospects and the value of our common stock.Our operations are subject to anti-corruption laws, including the US Foreign Corrupt Practices Act (FCPA), the UK43Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsBribery Act and other anti-corruption laws that apply in countries where we do business. The FCPA, UK Bribery Act and these other laws generally prohibitus, our employees and our intermediaries from making prohibited payments to government officials or other persons to obtain or retain business or gain someother business advantage. The CONVERT study includes more than 125 sites in 18 countries, and we conducted the 312 study and plan to conduct theWILLOW study, our global phase 2 study of INS1007 in non-CF bronchiectasis, at a broad range of trial sites around the world. Certain of these jurisdictionspose a risk of potential FCPA violations, and we have relationships with third parties whose actions could potentially subject us to liability under the FCPAor local anti-corruption laws. In addition, we cannot predict the nature, scope or effect of future regulatory requirements to which our international operationsmight be subject or the manner in which existing laws might be administered or interpreted.We are also subject to other laws and regulations governing our international operations, including regulations administered by the US Departmentof Commerce’s Bureau of Industry and Security, the US Department of Treasury’s Office of Foreign Assets Control, and various non-US government entities,including applicable export control regulations, economic sanctions on countries and persons, customs requirements, currency exchange regulations andtransfer pricing regulations (collectively, Trade Control laws).We may not be effective in ensuring our compliance with all applicable anti-corruption laws, including the FCPA or other legal requirements,including Trade Control laws. If we are not in compliance with the FCPA and other anti-corruption laws or Trade Control laws, we may be subject to criminaland civil penalties, disgorgement and other sanctions and remedial measures, and legal expenses, which could have an adverse impact on our business,financial condition, results of operations and prospects and the value of our common stock. Likewise, even an investigation by US or foreign authorities ofpotential violations of the FCPA other anti-corruption laws or Trade Control laws could have an adverse impact on our reputation, business, financialcondition, results of operations and prospects and the value of our common stock.If another party obtains orphan drug exclusivity for a product that is essentially the same as a product we are developing for a particular indication, wemay be precluded or delayed from commercializing the product in that indication.Under the ODA, the FDA may grant orphan drug designation to drugs intended to treat a rare disease or condition. The company that obtains the firstregulatory approval from the FDA for a designated orphan drug for a rare disease generally receives marketing exclusivity for use of that drug for thedesignated condition for a period of seven years. Similar laws exist in the EU with a term of ten years. See Business - Government Regulation - Orphan DrugDesignation in Item 1 of Part I of this 10-K for additional information. If a competitor obtains approval of the same drug for the same indication or diseasebefore us, and the FDA grants such orphan drug exclusivity, we would be prohibited from obtaining approval for our product for seven or more years, unlessour product can be shown to be clinically superior. In addition, even if we obtain orphan exclusivity, the FDA may approve another product during ourorphan exclusivity period for the same indication under certain circumstances.Our research, development and manufacturing activities used in the production of ARIKAYCE and our product candidates involve the use of hazardousmaterials, which could expose us to damages, fines, penalties and sanctions and materially adversely affect our results of operations and financialcondition.We are subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures and thehandling, use, storage, treatment and disposal of hazardous materials and wastes. Our research and development program and manufacturing activities forARIKAYCE and our product candidates involve the controlled use of hazardous materials and chemicals. We generally contract with third parties for thedisposal of these materials and wastes. Although we strive to comply with all pertinent regulations, the risk of environmental contamination, damage tofacilities or injury to personnel from the accidental or improper use or control of these materials remains. In addition to any liability we could have for anymisuse by us of hazardous materials and chemicals, we could also potentially be liable for activities of our CMOs or other third parties. Any such liability, oreven allegations of such liability, could materially adversely affect our results of operations and financial condition. We also could incur significant costs asa result of civil or criminal fines and penalties.In addition, we may incur substantial costs to comply with current or future environmental, health and safety laws and regulations. These current orfuture laws and regulations may impair our research, development or production efforts. Failure to comply with these laws and regulations also may result insubstantial fines, penalties or other sanctions.Risks Related to Our Financial Condition and Need for Additional CapitalWe have a history of operating losses, expect to incur operating losses for the foreseeable future and may never achieve or maintain profitability.44Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsWe have incurred losses each previous year of our operation, except in 2009, when we sold our manufacturing facility and certain other assets toMerck, and we did not generate significant revenue during the years ended December 31, 2018, 2017 or 2016. As of December 31, 2018, our accumulateddeficit was $1,282.2 million. For the years ended December 31, 2018, 2017 and 2016, our consolidated net loss was $324.3 million, $192.6 million and$176.3 million, respectively. Our ability to generate revenue will depend on the success of commercial sales of ARIKAYCE; however, we do not anticipateour revenue from the sale of ARIKAYCE will be sufficient for us to become profitable without reductions in our operating expenses. Despite our recentlaunch of ARIKAYCE in the US, we expect to continue to incur substantial operating expenses, and resulting operating losses, for the foreseeable future aswe: •initiate or continue clinical studies of our product candidates;•initiate a post-marketing clinical trial of ARIKAYCE, as required by the FDA;•seek to discover or in-license additional product candidates;•seek regulatory approvals for ARIKAYCE in foreign markets;•scale-up manufacturing capabilities for future ARIKAYCE production, including the build-out of production capacity at Patheon and processimprovements in order to manufacture at a commercial scale; and•enhance operational, compliance, financial, quality and information management systems and hire more personnel, including personnel to supportour commercialization efforts and development of our product candidates.Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis.We may need to raise additional funds to continue our operations, but we face uncertainties with respect to our ability to access capital.Our operations have consumed substantial amounts of cash since our inception. We expect to expend substantial financial resources tocommercialize ARIKAYCE, including expenditures on product sales, marketing, manufacturing and distribution, fund the confirmatory post-marketing studyand continue research and development of and, where applicable, seek regulatory approval for ARIKAYCE and our product candidates. We may need to raiseadditional capital to fund these activities, including due to changes in our product development plans or misjudgment of expected costs, to fund corporatedevelopment, to maintain our intellectual property portfolio or to resolve litigation. As of December 31, 2018, we had $495.1 million of cash and cashequivalents on hand. Our operating expenses, capital expenditures and long-term investments were significantly higher in 2018 than in 2017, reflecting ourinvestment in the build-out of our commercial organization to support global expansion activities for ARIKAYCE, including the launch of ARIKAYCE inthe US in the fourth quarter of 2018, the build-up of third-party manufacturing capacity and manufacture of commercial inventory, which includes capitaland long-term investments, and continued investment in research and development as well as selling, general and administrative expenses. We do not knowwhether additional financing will be available when needed, or, if available, whether the terms will be favorable. If adequate funds are not available to uswhen needed, we may be forced to delay, restrict or eliminate all or a portion of our development programs or commercialization efforts.We have outstanding indebtedness in the form of convertible senior notes, and may incur additional indebtedness in the future, which could adverselyaffect our financial position, prevent us from implementing our strategy, and dilute the ownership interest of our existing shareholders. In January 2018, we completed an underwritten public offering of 1.75% convertible senior notes due 2025 (the Convertible Notes). TheConvertible Notes may be convertible into common stock at an initial conversion rate of 25.5384 shares of common stock per $1,000 principal amount ofConvertible Notes. We sold $450.0 million aggregate principal amount of the Convertible Notes, including the exercise in full of the underwriters’ option topurchase additional Convertible Notes, resulting in net proceeds of approximately $435.8 million. Holders of the Convertible Notes may convert theirConvertible Notes at their option at any time prior to the close of business on the business day immediately preceding October 15, 2024 only under certaincircumstances. On or after October 15, 2024 until the close of business on the second scheduled trading day immediately preceding the maturity date, holdersmay convert their Convertible Notes at any time. Upon conversion of the Convertible Notes, we may deliver cash, shares of our common stock or acombination of cash and shares of our common stock, at our election.The degree to which we are leveraged could have negative consequences, such as the following:•we may be more vulnerable to economic downturns, less able to withstand competitive pressures, and less flexible in responding to changingeconomic conditions;•our ability to obtain financing in the future may be limited;45Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contents•a substantial portion of our cash flows from operations in the future may be required for the payment of the principal amount of the ConvertibleNotes when they or any additional indebtedness become due;•we may elect to make cash payments upon conversion of the Convertible Notes, which would reduce our available cash. Our ability to pay principal or interest on or, if desired, to refinance our indebtedness, including the Convertible Notes, depends on our futureperformance, which is subject to economic, financial, competitive and other factors, some of which are beyond our control. Our business may not generatecash flow from operations in the future sufficient to satisfy any obligations under the Convertible Notes to make cash payments to noteholders or ourobligations under any future indebtedness we may incur. If we are unable to generate such cash flow, we may be required to delay, restrict or eliminate all or aportion of our development programs or commercialization efforts or refinance or obtain additional equity capital on terms that may be onerous or highlydilutive. If we do not meet our debt obligations, it could materially adversely affect our results of operations, financial condition and the value of ourcommon stock. The conversion of some or all of the Convertible Notes will dilute the ownership interests of our existing shareholders to the extent we deliver sharesupon their conversion. Any sales in the public market of the common stock issuable upon such conversion could adversely affect prevailing market prices ofour common stock. In addition, the existence of the Convertible Notes may encourage short selling by market participants because the conversion of theConvertible Notes could be used to satisfy short positions, or anticipated conversion of the Convertible Notes into shares of our common stock could depressthe price of our common stock. The accounting method for the Convertible Notes may have an adverse effect on our reported financial results. Accounting guidance requires that we separately account for the liability and equity components of the Convertible Notes because they may besettled entirely or partially in cash upon conversion in a manner that reflects our economic interest cost. As a result, the equity component of the ConvertibleNotes is required to be included in the additional paid-in capital section of shareholders’ equity on our consolidated balance sheet, and the value of theequity component is treated as original issue discount for purposes of accounting for the debt component of the Convertible Notes. We may report greater netloss (or lower net income) in our financial results because this guidance requires interest to include both the current period’s amortization of the debtdiscount and the instrument’s coupon interest, which could adversely affect our reported or future financial results, the market price of our common stock andthe trading price of the Convertible Notes. Holders may convert their Convertible Notes at their option at any time prior to the close of business on the business day immediately precedingOctober 15, 2024 only under certain circumstances. For example, holders may convert their Convertible Notes at their option during any quarter commencingafter the quarter ending March 31, 2018 (and only during such quarter) if the last reported sale price of our common stock for at least 20 trading days (whetheror not consecutive) during a period of 30 consecutive trading days ending on the last trading day of the immediately preceding quarter is greater than orequal to 130% of the conversion price on each applicable trading day. If the Convertible Notes become convertible prior to October 15, 2024, we may berequired to reclassify our Convertible Notes and the related debt issuance costs as current liabilities and certain portions of our equity outside of equity tomezzanine equity, which would have an adverse impact on our reported financial results for such quarter, and could have an adverse impact on the marketprice of our common stock and the trading price of the Convertible Notes.Intangible assets comprised approximately 10% of our total assets as of December 31, 2018. A reduction in the value of our intangible assets could have amaterial adverse effect on our results of operations, financial condition and the value of our common stock.As a result of the merger with Transave in 2010, we recorded an intangible in-process research and development (IPRD) asset of $77.9 million andgoodwill of $6.3 million on our balance sheet. As a result of the clinical hold on ARIKAYCE announced in late 2011, we recorded a charge of $26.0 millionin the fourth quarter of 2011 that reduced the value of IPRD to $58.2 million and reduced goodwill to zero. In addition, in September 2018 we recorded anadditional $1.7 million in intangible assets related to a milestone to PARI as a result of FDA approval of ARIKAYCE. As of December 31, 2018, the balanceof these intangibles, net of amortization was $57.0 million and $1.7 million, respectively. Future activities or events could result in additional write-downs ofthese intangible assets, which could materially adversely affect our results of operations, financial condition and the value of our common stock.We may be unable to use certain of our net operating losses and other tax assets.We have substantial tax loss carry forwards for US federal income tax and state income tax purposes, and beginning in46Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contents2015, we had tax loss carry forwards in Ireland as well. In general, our net operating losses and tax credits have been fully offset by a valuation allowance dueto uncertainties surrounding our ability to realize these tax benefits. In particular, our ability to fully use certain US tax loss carry forwards and generalbusiness tax credit carry forwards recorded prior to December 2010 to offset future income or tax liability is limited under section 382 of the Internal RevenueCode of 1986, as amended (the Code). Changes in the ownership of our stock, including those resulting from the issuance of shares of our common stockofferings or upon exercise of outstanding options, may limit or eliminate our ability to use certain net operating losses and tax credit carry forwards in thefuture.Risks Related to Ownership of Our Common StockThe market price of our stock has been and may continue to be highly volatile, which could lead to shareholder litigation against us.Our common stock is listed on the Nasdaq Global Select Market under the ticker symbol “INSM”. The market price of our stock has been and maycontinue to be highly volatile and could be subject to wide fluctuations in price in response to various factors, including those discussed herein, many ofwhich are beyond our control. In addition, the stock market has from time to time experienced extreme price and volume fluctuations, which haveparticularly affected the market prices for emerging biotechnology and pharmaceutical companies like us, and which have often been unrelated to theiroperating performance.Historically, when the market price of a stock has been volatile, shareholders are more likely to institute securities and derivative class actionlitigation against the issuer of such stock. We previously faced a shareholder suit following a decline in our stock price. If any of our shareholders bring alawsuit against us in the future, it could have a material adverse effect on our business. We have insurance policies related to some of the risks associated withour business, including directors’ and officers’ liability insurance policies; however, our insurance coverage may not be sufficient and our insurance carriersmay not cover all claims in a given litigation. If we are not successful in our defense of claims asserted in shareholder litigation, those claims are not coveredby insurance or they exceed our insurance coverage, we may have to pay damage awards, indemnify our executive officers, directors and third parties fromdamage awards that may be entered against them and pay our and their costs and expenses incurred in defense of, or in any settlement of, such claims. Inaddition, such shareholder suits could divert the time and attention of management from our business.Certain provisions of Virginia law, our articles of incorporation and amended and restated bylaws and arrangements between us and our employees couldhamper a third-party’s acquisition of, or discourage a third-party from attempting to acquire control of us.Certain provisions of Virginia law, our articles of incorporation and amended and restated bylaws and arrangements with our employees couldhamper a third-party’s acquisition of, or discourage a third-party from attempting to acquire control of, us or limit the price that investors might be willing topay for shares of our common stock. These provisions or arrangements include:•The ability to issue preferred stock with rights senior to those of our common stock without any further vote or action by the holders of our commonstock. The issuance of preferred stock could decrease the amount of earnings and assets available for distribution to the holders of our common stockor could adversely affect the rights and powers, including voting rights, of the holders of our common stock. In certain circumstances, such issuancecould have the effect of decreasing the market price of our common stock.•The existence of a staggered board of directors in which there are three classes of directors serving staggered three-year terms, thus expanding thetime required to change the composition of a majority of directors.•The requirement that shareholders provide advance notice when nominating director candidates to serve on our Board of Directors.•The inability of shareholders to convene a shareholders’ meeting without the chairman of the board, the president or a majority of the board ofdirectors first calling the meeting.•The prohibition against entering into a business combination with the beneficial owner of 10% or more of our outstanding voting stock for a periodof three years after the 10% or greater owner first reached that level of stock ownership, unless certain criteria are met.•In addition to severance agreements with our officers and provisions in our incentive plans that permit acceleration of equity awards upon a changein control, a severance plan for eligible full-time employees that provides such employees with severance equal to six months of their then-currentbase salaries in connection with a termination of employment without cause upon, or within 18 months following, a change in control.47Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsWe previously had a shareholder rights plan, or “poison pill,” which expired in May 2011. Under Virginia law, our Board of Directors mayimplement a new shareholders’ rights plan without shareholder approval. Our Board of Directors intends to regularly consider this matter, even in the absenceof specific circumstances or takeover proposals, to facilitate its future ability to quickly and effectively protect shareholder value.48Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsITEM 1B. UNRESOLVED STAFF COMMENTSNone.49Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsITEM 2. PROPERTIESWe currently lease 56,617 square feet of laboratory and office space in Bridgewater, New Jersey. The initial term of the lease will expire inNovember 2019. We do not intend to exercise the option to extend the lease beyond the initial term. In September 2018, the Company entered into a newlease for 117,022 square feet of office space for our new corporate headquarters in Bridgewater. We have a one-time option to expand the new leased premisesby up to 50,000 square feet prior to the fifth anniversary of the initial lease commencement. The initial term of the new lease will expire in 2030.We also lease additional laboratory space located in Bridgewater, NJ for which the initial lease term expires in September 2021. In October 2018,the Company expanded this lease to a total of 28,002 square feet. In addition, we lease office space in Ireland, the Netherlands and Japan.ITEM 3. LEGAL PROCEEDINGSFrom time to time, we are a party to various lawsuits, claims and other legal proceedings that arise in the ordinary course of business. While theoutcomes of these matters are uncertain, management does not expect that the ultimate costs to resolve these matters will have a material adverse effect on ourconsolidated financial position, results of operations or cash flows.ITEM 4. MINE SAFETY DISCLOSURESNot applicable.50Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsPART IIITEM 5. MARKET FOR REGISTRANT'S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITYSECURITIESOur trading symbol is "INSM." Our common stock currently trades on the Nasdaq Global Select Market.On February 15, 2019, the last reported sale price for our common stock on the Nasdaq Global Select Market was $27.07 per share. As ofFebruary 15, 2019, there were 137 holders of record of our common stock.We have never declared or paid cash dividends on our common stock. We anticipate that we will retain all earnings, if any, to support operationsand to finance the growth and development of our business for the foreseeable future. Any future determination as to the payment of dividends will bedependent upon these and any contractual or other restrictions to which we may be subject and, to the extent permissible thereunder, will be at the solediscretion of our board of directors and will depend on our financial condition, results of operations, capital requirements and other factors our board ofdirectors deems relevant at that time.51Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsCOMPARISON OF 5 YEAR CUMULATIVE TOTAL RETURN*Among Insmed Incorporated, the NASDAQ Composite Index,the S&P 500 Index, the NASDAQ Pharmaceutical Index and the NASDAQ Biotechnology Index_________________________________* $100 invested on 12/31/13 in stock or index, including reinvestment of dividends.Fiscal year ending December 31.Copyright© 2019 Standard & Poor's, a division of S&P Global. All rights reserved.ITEM 6. SELECTED FINANCIAL DATAThe following selected financial data reflects our consolidated statements of operations and consolidated balance sheets for and as of the yearsended December 31, 2018, 2017, 2016, 2015 and 2014. The data below should be read in conjunction with, and is qualified by reference to, Management'sDiscussion and Analysis of Financial Condition and Results of Operations and our consolidated financial statements and notes thereto contained elsewherein this Annual Report on Form 10-K.52Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contents Year Ended December 31,2018 2017 2016 2015 2014(in thousands, except per share data)Statement of Operations Data: Revenues$9,835 $— $— $— $—Costs and expenses: Cost of product revenues (excluding amortization of intangibleassets)2,423 — — — —Research and development145,283 109,749 122,721 74,277 56,292Selling, general and administrative168,218 79,171 50,679 43,216 31,073 Amortization of intangible assets1,249 — — — —Total costs and expenses317,173 188,920 173,400 117,493 87,365Operating loss(307,338) (188,920) (173,400) (117,493) (87,365)Investment income10,341 1,624 604 261 58Interest expense(25,472) (5,925) (3,498) (2,889) (2,415)Loss on extinguishment of debt(2,209) — — — —Other income (expense), net602 300 119 (33) 141Loss before income taxes(324,076) (192,921) (176,175) (120,154) (89,581)Income tax provision (benefit)201 (272) 98 (1,971) (10,422)Net loss$(324,277) $(192,649) $(176,273) $(118,183) $(79,159)Basic and diluted net loss per share$(4.22) $(2.89) $(2.85) $(2.02) $(1.84)Weighted average basic and diluted common shares outstanding76,889 66,576 61,892 58,633 43,095Balance Sheet Data: Cash and cash equivalents$495,072 $381,165 $162,591 $282,876 $159,226Total assets$604,556 $462,047 $237,956 $356,556 $230,864Current portion of long-term debt$— $— $— $3,113 $—Debt, long-term$316,558 $55,567 $54,791 $22,027 $24,856Total shareholders' equity$208,266 $361,059 $154,483 $311,698 $186,23753Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsITEM 7. MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS The following discussion also should be read in conjunction with our consolidated financial statements and the notes thereto contained elsewherein this Annual Report on Form 10-K. This discussion contains forward-looking statements that involve risks and uncertainties. As a result of many factors,such as those set forth under the section entitled Risk Factors, Cautionary Note Regarding Forward-Looking Statements and elsewhere herein, our actualresults may differ materially from those anticipated in these forward-looking statements.EXECUTIVE OVERVIEWWe are a global biopharmaceutical company on a mission to transform the lives of patients with serious and rare diseases. Our first commercialproduct, ARIKAYCE (amikacin liposome inhalation suspension), received accelerated approval in the United States (US) on September 28, 2018 for thetreatment of Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen for adult patients with limited or noalternative treatment options in a refractory setting as defined by patients who do not achieve negative sputum cultures after a minimum of 6 consecutivemonths of a multidrug background regimen therapy. MAC lung disease is a rare and often chronic infection that can cause irreversible lung damage and canbe fatal. Our clinical-stage pipeline includes INS1007 and INS1009. INS1007 is a novel oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP1) withtherapeutic potential in non-cystic fibrosis (non-CF) bronchiectasis and other inflammatory diseases. INS1009 is an inhaled formulation of a treprostinilprodrug that may offer a differentiated product profile for rare pulmonary disorders, including pulmonary arterial hypertension (PAH). We have legal entitiesin the US, Ireland, Germany, France, the United Kingdom (UK), the Netherlands, Japan and Bermuda.We have not generated significant revenue since inception, and through December 31, 2018, we had an accumulated deficit of $1,282.2 million.We have financed our operations primarily through the public offerings of our equity securities and debt financings. Although it is difficult to predict ourfuture funding requirements, based upon our current operating plan, we anticipate that our cash and cash equivalents as of December 31, 2018 will enable usto fund our operations for at least the next 12 months.We expect that over the next few years we will continue to incur losses from operations due to, among other things, research and developmentexpenses in connection with our ongoing and future clinical trials and expenses related to the commercial launch of ARIKAYCE globally, if approvedoutside the US.APPROVED PRODUCT - ARIKAYCEARIKAYCE is our first approved product. Accelerated approval of ARIKAYCE was supported by preliminary data from our CONVERT study, aglobal Phase 3 study evaluating the safety and efficacy of ARIKAYCE in adult patients with refractory MAC lung disease, using achievement of sputumculture conversion (defined as three consecutive negative monthly sputum cultures) by Month 6 as the primary endpoint. Patients who achieved sputumculture conversion by Month 6 continued in the CONVERT study for an additional 12 months of treatment following the first monthly negative sputumculture in order to assess the durability of culture conversion, as defined by patients that have completed treatment and continued in the CONVERT study offall therapy for three months. The CONVERT study is ongoing.Patients who did not culture convert by Month 6 may have been eligible to enroll in our 312 study, an open-label extension study for these non-converting patients who completed six months of treatment in the CONVERT study. The primary objective of the 312 study was to evaluate the long-termsafety and tolerability of ARIKAYCE in combination with a standard multi-drug regimen. The secondary endpoints of the 312 study included evaluating theproportion of subjects achieving culture conversion (defined in the same way as the CONVERT study) by Month 6 and the proportion of subjects achievingculture conversion by Month 12, which was the end of treatment. The 312 study has completed.As a condition of accelerated approval, we must conduct a post-approval confirmatory clinical trial. The required confirmatory trial, which iscurrently under discussion with the FDA, is proposed to be a randomized, double-blind, placebo-controlled clinical trial to assess and describe the clinicalbenefit of ARIKAYCE in patients with MAC lung disease. The trial will evaluate the effect of ARIKAYCE on a clinically meaningful endpoint, as comparedto an appropriate control, in the intended patient population of patients with MAC lung disease. Pursuant to the timetable agreed upon with the FDA, thestudy protocol is expected to be finalized during the first half of 2019, with trial results to be reported by 2024. Continued approval of ARIKAYCE will becontingent upon verification and description of clinical benefit in this study.PIPELINE PROGRESS INS100754Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contents INS1007 is a small molecule, oral, reversible inhibitor of DPP1, which we licensed from AstraZeneca in October 2016. DPP1 is an enzymeresponsible for activating neutrophil serine proteases in neutrophils when they are formed in the bone marrow. Neutrophils are the most common type ofwhite blood cell and play an essential role in pathogen destruction and inflammatory mediation. Neutrophils contain the neutrophil serine proteases(including neutrophil elastase, proteinase 3, and cathepsin G) that have been implicated in a variety of inflammatory diseases. In chronic inflammatory lungdiseases, neutrophils accumulate in the airways and release active neutrophil serine proteases in excess that cause lung destruction and inflammation.INS1007 may decrease the damaging effects of inflammatory diseases, such as non-CF bronchiectasis, by inhibiting DPP1 and its activation of neutrophilserine proteases. Non-CF bronchiectasis is a progressive pulmonary disorder in which the bronchi become permanently dilated due to chronic inflammationand infection. Currently, there is no cure, and we are not aware of any FDA-approved therapies specifically indicated for non-CF bronchiectasis. The WILLOW Study The WILLOW study is a global phase 2, randomized, double-blind, placebo-controlled, parallel group, multi-center clinical study to assess theefficacy, safety and tolerability, and pharmacokinetics of INS1007 administered once daily for 24 weeks in subjects with non-CF bronchiectasis. Wecommenced enrollment in the WILLOW study in December 2017 and we expect to complete enrollment in mid-2019. In addition, we are exploring thepotential of INS1007 in various neutrophil-driven inflammatory conditions. INS1009 INS1009 is an investigational inhaled treprostinil prodrug formulation that has the potential to address certain of the current limitations of existingprostanoid therapies. We believe that INS1009 prolongs duration of effect and may provide PAH patients with greater consistency in pulmonary arterialpressure reduction over time. Current inhaled prostanoid therapies must be dosed four to nine times per day for the treatment of PAH. Reducing dosefrequency has the potential to ease patient burden and improve compliance. Additionally, we believe that INS1009 may be associated with fewer side effects,including elevated heart rate, low blood pressure, and severity and/or frequency of cough, associated with high initial drug levels and local upper airwayexposure when using current inhaled prostanoid therapies. We believe INS1009 may offer a differentiated product profile for rare pulmonary disorders,including PAH, and we are currently evaluating our options to advance its development, including exploring its use as an inhaled dry powder formulation. Other Development ActivitiesOur earlier-stage pipeline includes preclinical compounds that we are evaluating in multiple rare diseases of unmet medical need, including grampositive pulmonary infections in CF, NTM lung disease and refractory localized infections involving biofilm. To complement our internal research anddevelopment, we actively evaluate in-licensing and acquisition opportunities for a broad range of rare diseases.KEY COMPONENTS OF OUR RESULTS OF OPERATIONSRevenuesProduct revenues consist primarily of net sales of ARIKAYCE in the US. In October 2018, we began shipping ARIKAYCE to our customers in theUS, which include specialty pharmacies and specialty distributors. We recognize revenue for product received by our customers net of allowances forcustomer credits, including estimated rebates, chargebacks, prompt pay discounts, returns, service fees, and government rebates, such as Medicaid rebates andMedicare Part D coverage gap reimbursements in the US. We also began recognizing revenue from sales to the French National Agency for Medicines andHealth Products Safety (ANSM), which granted ARIKAYCE a Temporary Authorizations for Use (Autorisation Temporaire d'Utilisation or ATU).Cost of product revenues (excluding amortization of intangible assets)Cost of product revenues (excluding amortization of intangible assets) consist primarily of direct and indirect costs related to the manufacturing ofARIKAYCE sold, including third-party manufacturing costs, packaging services, freight, allocation of overhead costs, and inventory adjustment charges, inaddition to royalty expenses due to PARI. We began capitalizing inventory upon FDA approval of ARIKAYCE.Research and Development (R&D) ExpensesR&D expenses consist of salaries, benefits and other related costs, including stock-based compensation, for personnel serving in our research anddevelopment functions, including medical affairs. Expenses also include other internal operating55Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentsexpenses, the cost of manufacturing our drug candidate(s) for clinical study, the cost of conducting clinical studies, and the cost of conducting preclinicaland research activities. In addition, our R&D expenses include payments to third parties for the license rights to products in development (prior to marketingapproval), such as for INS1007. Our expenses related to manufacturing our drug candidate(s) for clinical study are primarily related to activities at contractmanufacturing organizations (CMOs) that manufacture our product candidates for our use, including purchases of active pharmaceutical ingredients. Ourexpenses related to clinical trials are primarily related to activities at contract research organizations that conduct and manage clinical trials on our behalf.Since 2011, we have focused our development activities principally on our proprietary, advanced liposomal technology designed specifically forinhaled therapies. Our development efforts in 2018 and 2017 principally related to the development of ARIKAYCE in NTM lung disease.Selling, General and Administrative (SG&A) ExpensesSG&A expenses consist primarily of salaries, benefits and other related costs, including stock-based compensation, for our non-employee directorsand personnel serving in our executive, finance and accounting, legal and compliance, commercial and pre-commercial, corporate development, field sales,information technology, program management and human resource functions. SG&A expenses also include professional fees for legal services, consultingservices, including pre-commercial planning activities such as non-branded disease awareness, insurance, board of director fees, tax and accounting services.Amortization of Intangible Assets Upon commercialization of ARIKAYCE, our intangible assets began to be amortized over their estimated useful lives. The fair values assigned toour intangible assets are based on estimates and assumptions we believe are reasonable based on available facts and circumstances. Unanticipated events orcircumstances may occur that require us to review the assets for impairment.Investment Income and Interest ExpenseInvestment income consists of interest and dividend income earned on our cash and cash equivalents. Interest expense consists primarily of theaccretion of debt discount, contractual interest costs and the amortization of debt issuance costs related to our accretion of debt. Debt discount is accreted,and debt issuance costs are amortized, to interest expense using the effective interest rate method over the term of the debt. Our balance sheet reflects debt,net of the debt discount, debt issuance costs paid to the lender, and other third-party costs. Unamortized debt issuance costs associated with extinguisheddebt are expensed in the period of the extinguishment.RESULTS OF OPERATIONSComparison of the Years Ended December 31, 2018 and 2017Overview - Operating ResultsOur operating results for the year ended December 31, 2018, included the following:•Total revenues of $9.8 million during the year ended December 31, 2018, as a result of the fourth quarter launch of ARIKAYCE, following US FDAapproval on September 28, 2018;•Cost of product revenues (excluding amortization of intangibles) of $2.4 million during the year ended December 31, 2018 related to sales ofARIKAYCE;•R&D expenses increased $35.5 million primarily resulting from an increase in external manufacturing expenses and higher compensation andrelated expenses due to an increase in headcount, as compared to the prior year;•SG&A expenses increased $89.0 million resulting from higher compensation and related expenses due to an increase in headcount, and an increasein consulting fees relating to pre-commercial planning activities in preparation for the launch of ARIKAYCE, as compared to the prior year;•Amortization of intangible assets of $1.2 million during the year ended December 31, 2018; and•Interest expense increased $19.5 million from the issuance of $450.0 million aggregate principal amount of 1.75% convertible senior notes due2025 (the Convertible Notes) in January 2018.Net loss for the year ended December 31, 2018 was $324.3 million, or $4.22 per share—basic and diluted, compared with a net loss of $192.6million, or $2.89 per share—basic and diluted, for the year ended December 31, 2017.56Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsRevenuesTotal revenue consists of net sales of ARIKAYCE, which was approved by the FDA on September 28, 2018 and launched in the US in October2018. The following table summarizes the sources of revenue for the year ended December 31, 2018 (in thousands): For the Year EndedDecember 31, 2018Net product revenues, US$9,265Net product revenues, France ATU570 Total revenues$9,835Cost of Product Revenues (excluding amortization of intangibles)Cost of product revenues (excluding amortization of intangible assets) consist primarily of direct and indirect costs related to the manufacturing ofARIKAYCE sold, including third-party manufacturing costs, packaging services, freight, allocation of overhead costs, and inventory adjustment charges, inaddition to royalty expenses due to PARI. We began capitalizing inventory upon FDA approval of ARIKAYCE. Cost of product revenues (excludingamortization of intangible assets) was $2.4 million during the year ended December 31, 2018.All product costs incurred prior to FDA approval of ARIKAYCE in September 2018 were expensed as R&D expenses. As mentioned above, our costof product revenues includes certain expenses which are fixed, other expenses that were incurred after FDA approval and royalties based on net sales. Weexpect our cost of product revenues (excluding amortization of intangible assets), as a percentage of total revenue, to decrease in 2019 as compared to thefourth quarter of 2018.R&D ExpensesR&D expenses for the years ended December 31, 2018 and 2017 were comprised of the following (in thousands): Years Ended December 31, Increase (decrease) 2018 2017 $ %External Expenses Clinical development and research $30,287 $40,511 $(10,224) (25.2)%Manufacturing 43,824 19,808 24,016 121.2%Regulatory, quality assurance, and medical affairs 12,290 7,308 4,982 68.2%Subtotal—external expenses $86,401 $67,627 $18,774 27.8%Internal Expenses Compensation and benefit related expenses $38,794 $27,689 $11,105 40.1%Stock-based compensation 9,395 6,491 2,904 44.7%Other internal operating expenses 10,693 7,942 2,751 34.6%Subtotal—internal expenses $58,882 $42,122 $16,760 39.8%Total $145,283 $109,749 $35,534 32.4%R&D expenses increased to $145.3 million during the year ended December 31, 2018 from $109.7 million in the same period in 2017. The $35.5million increase was primarily due to an increase of $24.0 million in external manufacturing expenses, specifically related to: pre-approval purchases ofARIKAYCE raw materials; pre-approval CMO expenses related to ARIKAYCE commercial inventory production; and construction costs relating to thebuild-out of a third-party CMO production facility. In addition, there was a $11.1 million increase in compensation and related expenses due to an increase inheadcount in the year ended December 31, 2018 as compared to the prior year period. These increases were partially offset by a decrease in clinicaldevelopment and research expenses related to the CONVERT and 312 clinical trials.During the year ended December 31, 2018, external R&D expenses of $86.4 million consisted of $69.2 million related to ARIKAYCE, $13.9million related to INS1007, and $3.3 million related to other research expenses. During the year ended December 31, 2017, external R&D expenses of $67.6million consisted of $54.6 million related to ARIKAYCE, $10.2 million related to INS1007, and $2.8 million related to other research expenses.57Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsSG&A ExpensesSG&A expenses for the year ended December 31, 2018 and 2017 were comprised of the following (in thousands): Years Ended December 31, Increase (decrease) 2018 2017 $ %Compensation and benefit related expenses $62,592 $23,218 $39,374 169.6%Stock-based compensation 16,845 11,582 5,263 45.4%Professional fees and other external expenses 70,248 30,700 39,548 128.8%Facility related and other internal expenses 18,533 13,671 4,862 35.6%Total SG&A expenses $168,218 $79,171 $89,047 112.5%SG&A expenses increased to $168.2 million during the year ended December 31, 2018 from $79.2 million in the same period in 2017. The $89.0million increase was primarily due to $39.4 million in higher compensation and related expenses due to an increase in headcount, including the hiring of ourfield force, and $39.5 million in professional fees relating to pre-commercial planning activities in preparation for the launch of ARIKAYCE, including non-branded disease awareness, patient support planning, field operations and other consulting fees.Amortization of Intangible AssetsAmortization of intangible assets for the year ended December 31, 2018 was $1.2 million and is comprised of amortization of acquired ARIKAYCER&D and amortization of the milestone paid to PARI for the FDA approval of ARIKAYCE.Interest ExpenseInterest expense was $25.5 million for the year ended December 31, 2018 as compared to $5.9 million for 2017. The $19.5 million increase ininterest expense in the year ended December 31, 2018 as compared to the prior year period relates to the issuance of $450.0 million aggregate principalamount of Convertible Notes in January 2018. The interest expense on the Convertible Notes is based on an effective interest rate of 7.6%.Income tax provision (benefit)The income tax provision (benefit) was $0.2 million and $(0.3) million for the years ended December 31, 2018 and 2017, respectively. The incometax provision for the year ended December 31, 2018 reflects the current income tax expense recorded as a result of taxable income in certain of oursubsidiaries in Europe and Japan. The income tax (benefit) for the year ended December 31, 2017 reflects the reversal of the valuation allowance related toalternative minimum tax (AMT) that we paid in 2009 and became refundable as a result of the Tax Act.On December 22, 2017, the US government enacted comprehensive tax legislation, referred to as the Tax Cuts and Jobs Act (the Tax Act). The TaxAct significantly revised US tax law by, among other provisions, lowering the US federal statutory corporate tax rate from 35% to 21%, imposing amandatory one-time transition tax on previously deferred foreign earnings, and eliminating or reducing certain income tax deductions. The Tax Act did nothave a material impact on our financial statements because our deferred temporary differences are fully offset by a valuation allowance and we did not haveany significant offshore earnings from which to record the mandatory transition tax.Comparison of the Years Ended December 31, 2017 and 2016Net LossNet loss for the year ended December 31, 2017 was $192.6 million, or $2.89 per share—basic and diluted, compared with a net loss of$176.3 million, or $2.85 per share—basic and diluted, for the year ended December 31, 2016. The $16.4 million increase in our net loss for the year endedDecember 31, 2017 as compared to the same period in 2016 was due to:•Decreased R&D expenses of $13.0 million primarily resulting from the $30.0 million upfront payment for the license agreement entered into withAstraZeneca for exclusive global rights to INS1007 in October 2016, offset in part by, an increase in expenses related to the WILLOW study andhigher compensation and related expenses due to an increase in headcount; and•Increased SG&A expenses of $28.5 million resulting from an increase in pre-commercial planning activities, including external consulting expenses,and higher compensation and related expenses due to an increase in headcount.58Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsIn addition, there was a $2.4 million increase in interest expense resulting from the increase in our debt in the second half of 2016.R&D ExpensesR&D expenses for the years ended December 31, 2017 and 2016 were comprised of the following (in thousands): Years Ended December 31, Increase (decrease) 2017 2016 $ %External Expenses Clinical development and research $40,511 $35,890 $4,621 12.9 %INS1007 license payment — 30,000 (30,000) (100.0)%Manufacturing 19,808 17,313 2,495 14.4 %Regulatory, quality assurance, and medical affairs 7,308 4,064 3,244 79.8 %Subtotal—external expenses $67,627 $87,267 $(19,640) (22.5)%Internal Expenses Compensation and benefit related expenses $27,689 $22,321 $5,368 24.0 %Stock-based compensation 6,491 6,192 299 4.8 %Other internal operating expenses 7,942 6,941 1,001 14.4 %Subtotal—internal expenses $42,122 $35,454 $6,668 18.8 %Total $109,749 $122,721 $(12,972) (10.6)%R&D expenses decreased to $109.7 million during the year ended December 31, 2017 from $122.7 million in the same period in 2016. The $13.0million decrease was due to a $30.0 million upfront payment under the AZ License Agreement related to INS1007 in October 2016 and a $3.7 milliondecrease in expenses relating to INS1009. These decreases were partially offset by a $10.2 million increase in raw materials purchases and expenses related tothe WILLOW trial for INS1007 and a $5.4 million increase in compensation and related expenses due to an increase in headcount. There was also an increaseof $3.2 million due to increased regulatory, quality assurance and medical affairs consulting expenses and medical grants.SG&A ExpensesSG&A expenses for the year ended December 31, 2017 and 2016 were comprised of the following (in thousands): Years Ended December 31, Increase (decrease) 2017 2016 $ %Compensation and benefit related expenses $23,218 $15,550 $7,668 49.3 %Stock-based compensation 11,582 11,841 (259) (2.2)%Professional fees and other external expenses 30,700 17,763 12,937 72.8 %Facility related and other internal expenses 13,671 5,525 8,146 147.4 %Total SG&A expenses $79,171 $50,679 $28,492 56.2 %SG&A expenses increased to $79.2 million during the year ended December 31, 2017 from $50.7 million in the same period in 2016. The $28.5million increase was due to an increase of $12.9 million in consulting fees relating to pre-commercial planning activities, primarily resulting from a one-timepayment in October 2017 related to the buy-down of future royalties payable to PARI on the global net sales of ARIKAYCE, an increase of $7.7 million dueto higher compensation costs related to an increase in headcount, and an increase of $8.1 million due to higher facility related expenses.Interest ExpenseInterest expense was $5.9 million during the year ended December 31, 2017 as compared to $3.5 million in the same period in 2016. The$2.4 million increase in interest expense in 2017 relates primarily to an increase in our borrowings from Hercules Capital (Hercules) in September andOctober of 2016. We entered into an Amended and Restated Loan Agreement (A&R Loan Agreement) with Hercules which increased our borrowing capacityby an additional $30.0 million to an aggregate total of $55.0 million. The increase in borrowings under the A&R Loan Agreement was used to fund theupfront payment owed under the AZ License Agreement for the exclusive global rights to INS1007.59Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsIncome tax (benefit) provisionThe income tax (benefit) provision was $(0.3) million and $0.1 million for the years ended December 31, 2017 and 2016, respectively. The incometax (benefit) for the year ended December 31, 2017 reflects the reversal of the valuation allowance related to AMT that we paid in 2009. As a result of the TaxAct, we recorded a noncurrent receivable to reflect the tax amount due to us in future periods relating to a refund due for the prior AMT paid. In addition, theincome tax (benefit) provision for the years ended December 31, 2017 and 2016 reflects current income tax expense recorded as a result of taxable income incertain of our subsidiaries in Europe.LIQUIDITY AND CAPITAL RESOURCESOverviewThere is considerable time and cost associated with developing potential pharmaceutical products to the point of regulatory approval andcommercialization. We commenced commercial shipments of ARIKAYCE in October 2018, and to date, have not generated significant revenue from sales ofARIKAYCE. In recent years, we have funded our operations through public offerings of equity securities and debt financings.In January 2018, we completed an underwritten public offering of $450.0 million aggregate principal amount of Convertible Notes, including theexercise in full of the underwriter's option to purchase additional Convertible Notes. Our net proceeds from the offering, after deducting underwritingdiscounts and commissions and other offering expenses of $14.2 million, were $435.8 million. In September 2017, we completed an underwritten public offering of 14,123,150 shares of our common stock, which included the underwriter’sexercise in full of its over-allotment option of 1,842,150 shares, at a price to the public of $28.50 per share. Our net proceeds from the sale of the shares, afterdeducting underwriting discounts and offering expenses of $24.8 million, were $377.7 million.We expect to continue to incur operating losses both in our US and certain international entities, as we plan to fund research and developmentactivities and commercial launch activities for ARIKAYCE. We may need to raise additional capital to fund our operations, including the continuedcommercialization of ARIKAYCE, future clinical trials related to ARIKAYCE, development of INS1007 and INS1009, and the potential development,acquisition, in-license or co-promotion of other products or product candidates that address orphan or rare diseases. We believe we currently have sufficientfunds to meet our financial needs for at least the next 12 months. We may opportunistically raise additional capital through equity or debt financing(s),strategic transactions or otherwise. We expect such additional funding, if any, would be used to continue to commercialize ARIKAYCE, to conduct furthertrials of ARIKAYCE, to develop our product candidates, or to pursue the license or purchase of other technologies or products or product candidates. In 2019,we plan to continue to support the commercial launch of ARIKAYCE in the US, to fund further clinical development of ARIKAYCE and INS1007, andsupport efforts to obtain regulatory approvals for ARIKAYCE outside the US. Our cash requirements in 2019 will be impacted by a number of factors, themost significant of which are expenses related to the commercialization efforts for ARIKAYCE, and to a lesser extent, expenses related to INS1007 and futureARIKAYCE clinical trials.Cash FlowsAs of December 31, 2018, we had cash and cash equivalents of $495.1 million, as compared with $381.2 million as of December 31, 2017. The$113.9 million increase was due primarily to the net cash proceeds from our issuance of Convertible Notes in January 2018, partially offset by cash used inoperating activities and, to a lesser extent, cash used in investing activities. Our working capital was $439.2 million as of December 31, 2018 as comparedwith $344.8 million as of December 31, 2017.Net cash used in operating activities was $258.0 million and $159.6 million for the years ended December 31, 2018 and 2017, respectively. Thenet cash used in operating activities during the years ended December 31, 2018 and 2017 was primarily for the pre-commercialization efforts and clinicalactivities related to ARIKAYCE, as well as general and administrative expenses. In addition, net cash used in operating activities during the year endedDecember 31, 2018 and 2017 included commercialization efforts and clinical trial expenses related to INS1007.Net cash used in investing activities was $14.8 million and $3.0 million for the years ended December 31, 2018 and 2017, respectively. The netcash used in investing activities during 2018 was primarily related to the investment in our long-term production capacity build-out at Patheon. The net cashused in investing activities during 2017 was primarily related to the investment in our long-term production capacity build-out at Patheon and for the buildout of our lab facility in Bridgewater,60Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsNew Jersey. We expect our net cash used in investing activities will increase in 2019 as compared to 2018 as a result of our continuing investment in thebuild-out of Patheon and our new headquarters facility.Net cash provided by financing activities was $386.7 million and $381.1 million for the years ended December 31, 2018 and 2017, respectively.Net cash provided by financing activities for the year ended December 31, 2018 included net cash proceeds of $435.8 million from our issuance ofConvertible Notes in January 2018 and cash proceeds from stock option exercises, partially offset by the February 2018 repayment of our outstanding debt toHercules in the amount of $55.0 million. Net cash provided by financing activities during 2017 included net cash proceeds of $377.7 million from ourissuance of 14.1 million shares of common stock in September 2017 and cash proceeds received from stock option exercises.Contractual ObligationsIn January 2018, we completed an underwritten public offering of $450.0 million aggregate principal amount of Convertible Notes pursuant to anindenture between the Company and Wells Fargo Bank, National Association, as trustee. Our net proceeds from the offering, after deducting underwritingdiscounts and commissions and other offering expenses of $14.2 million, were approximately $435.8 million. The Convertible Notes bear interest payablesemiannually in arrears on January 15 and July 15 of each year, beginning on July 15, 2018. The Convertible Notes mature on January 15, 2025, unlessearlier converted, redeemed, or repurchased. The Convertible Notes are convertible into common stock of the Company under certain circumstancesdescribed in the indenture. For more information, see Note 7 - Debt in our notes to the consolidated financial statements.We have an operating lease for office and laboratory space located in Bridgewater, NJ, our corporate headquarters, for which the initial lease termexpires in November 2019. Future minimum rental payments under this lease total approximately $1.0 million. In July 2016, we signed an operating lease foradditional laboratory space located in Bridgewater, NJ, for which the initial lease term expires in September 2021, and in October 2018, the Companyexpanded this lease. Future minimum rental payments under this, and the initial lease, are $3.3 million.In September 2018, we entered into an agreement (the Lease) with Exeter 700 Route 202/206, LLC to lease approximately 117,000 rentable squarefeet of office space located at 700 Route 202/206, Bridgewater, New Jersey for our future headquarters. Subject to certain conditions, we have the one-timeoption to expand the leased premises by up to 50,000 rentable square feet, exercisable prior to the fifth anniversary of the Commencement Date (as definedbelow). The Lease provides for a commencement date of the earlier of (1) September 1, 2019, subject to completion of certain improvements by specifieddates, and (2) the date on which we take possession of the premises to commence its business operations therein (the Commencement Date). The initial Leaseterm runs 130 months from the Commencement Date (plus any partial month from the Commencement Date until the first day of the next full calendar monthduring the term) and we have the option to extend that term for up to three additional five-year periods. In addition, we are also responsible for operatingexpenses and taxes pursuant to the Lease. Future minimum payments under the Lease during the initial Lease Term are expected to approximate $32.3million. The Lease contains customary default provisions, including those relating to payment defaults, performance defaults and events of bankruptcy.In February 2014, we entered into a contract manufacturing agreement with Therapure for the manufacture of ARIKAYCE, on a non-exclusivebasis, at a 200 kg scale. Pursuant to the agreement, we collaborated with Therapure to construct a production area for the manufacture of ARIKAYCE inTherapure's existing manufacturing facility in Canada. The agreement has an initial term of five years from the first date on which Therapure deliversARIKAYCE to us after we obtain permits related to the manufacture of ARIKAYCE, and will renew automatically for successive periods of two years each,unless terminated by either party by providing the required two years' prior written notice to the other party. Under the agreement, we are obligated to paycertain minimum amounts for the batches of ARIKAYCE produced each calendar year.In September 2015, we entered into a Commercial Fill/Finish Services Agreement (the Fill/Finish Agreement) with Althea, for Althea to produce,on a non-exclusive basis, ARIKAYCE in finished dosage form at a 50 kg scale. Under the Fill/Finish Agreement, we are obligated to pay a minimum of$2.7 million for the batches of ARIKAYCE produced each calendar year during the term of the Fill/Finish Agreement. The Fill/Finish Agreement becameeffective as of January 1, 2015, and following an extension in 2018, the agreement remains in effect through December 31, 2021. The Fill/Finish Agreementmay be extended for additional two-year periods upon mutual written agreement of the Company and Althea at least one year prior to the expiration of itsthen-current term.We currently have a licensing agreement with PARI for the use of the optimized Lamira Nebulizer System for delivery of ARIKAYCE in treatingpatients with NTM lung infections, CF and bronchiectasis. Under the licensing agreement, we have rights under several US and foreign issued patents, andpatent applications involving improvements to the optimized Lamira Nebulizer System, to exploit such system with ARIKAYCE for the treatment of suchindications, but we cannot manufacture such nebulizers except as permitted under our Commercialization Agreement with PARI. Under the licensing61Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentsagreement, we paid PARI an upfront license fee and milestone payments. Upon FDA acceptance of our New Drug Application and the subsequent FDAapproval of ARIKAYCE, we paid PARI additional milestone payments of €1.0 million and €1.5 million, respectively. In addition, PARI is entitled to receivea future milestone payment of €0.5 million in cash based on achievement of first receipt of marketing approval in a major EU country for ARIKAYCE and thedevice. In October 2017, we exercised an option to buy-down the royalties payable to PARI, which was included within selling, general and administrativeexpenses in the fourth quarter of 2017. PARI is now entitled to receive royalty payments in the mid-single digits on the annual global net sales ofARIKAYCE, pursuant to the licensing agreement, subject to certain specified annual minimum royalties.In July 2014, we entered into a Commercialization Agreement with PARI for the manufacture and supply of the Lamira Nebulizer Systems andrelated accessories (the Device) as optimized for use with ARIKAYCE. Under the Commercialization Agreement, PARI manufactures the Device except in thecase of certain defined supply failures, when the Company will have the right to make the Device and have it made by third parties (but not certain thirdparties deemed under the Commercialization Agreement to compete with PARI). The Commercialization Agreement has an initial term of 15 years that beganin October 2018 (the Initial Term). The term of the Commercialization Agreement may be extended by us for an additional five years by providing writtennotice to PARI at least one year prior to the expiration of the Initial Term.In October 2017, we entered into certain agreements with Patheon related to the increase of our long-term production capacity for ARIKAYCE. Theagreements provide for Patheon to manufacture and supply ARIKAYCE for our anticipated commercial needs. Under these agreements, we are required todeliver to Patheon the required raw materials, including active pharmaceutical ingredients, and certain fixed assets needed to manufactureARIKAYCE. Patheon's supply obligations will commence once certain technology transfer and construction services are completed. Our manufacturing andsupply agreement with Patheon will remain in effect for a fixed initial term, after which it will continue for successive renewal terms unless either we orPatheon have given written notice of termination. The technology transfer agreement will expire when the parties agree that the technology transfer serviceshave been completed. The agreements may also be terminated under certain other circumstances, including by either party due to a material uncured breachof the other party or the other party’s insolvency. These early termination clauses may reduce the amounts due to the relevant parties. The investment in ourlong-term production capacity build-out, including under the Patheon agreements and related agreements or purchase orders with third parties for rawmaterials and fixed assets, is estimated to be approximately $60 million.As of December 31, 2018, future payments under our long-term debt agreements, minimum future payments under non-cancellable leases andminimum future payment obligations are as follows: As of December 31, 2018Payments Due By Period Total Less than1 year 1 - 3 Years 3 - 5 Years More than 5Years (in thousands)Debt obligations Debt maturities $450,000 $— $— $— $450,000Contractual interest 51,209 7,875 15,750 15,750 11,834Capital leases 32,250 244 5,944 4,370 21,692Operating leases 6,425 2,881 3,543 1 —Purchase obligations 86,383 13,029 10,579 7,650 55,125Total contractual obligations $626,267 $24,029 $35,816 $27,771 $538,651This table does not include: (a) any milestone payments which may become payable to third parties under our license and collaborationagreements as the timing and likelihood of such payments are not known; (b) the royalty payments specified below, as the amounts of such payments, timingand/or the likelihood of such payments are not known; (c) contracts that are entered into in the ordinary course of business which are not material in theaggregate in any period presented above; and (d) any payments related to the agreements mentioned below.We entered into a services agreement with Syneos Health (Syneos) pursuant to which we retained Syneos to perform implementation andmanagement services in connection with the WILLOW study. We may terminate the services agreement or any work order for any reason and without causewith 30 days' written notice. Either party may terminate the agreement in the event of a material breach or bankruptcy petition by the other party or, if anyapproval from a regulatory authority is revoked, suspended or expires without renewal. We anticipate that aggregate costs relating to all work orders for theWILLOW study will be approximately $21 million over the period of the study.62Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsIn October 2016, we entered into the AZ License Agreement, pursuant to which AstraZeneca granted us exclusive global rights for the purpose ofdeveloping and commercializing AZD7986 (which we renamed INS1007). In consideration of the licenses and other rights granted by AstraZeneca, we madean upfront payment of $30.0 million, which was included as research and development expense in the fourth quarter of 2016. We are obligated to make aseries of contingent milestone payments to AstraZeneca totaling up to an additional $85.0 million upon the achievement of clinical development andregulatory filing milestones. If we elect to develop INS1007 for a second indication, we will be obligated to make an additional series of contingentmilestone payments totaling up to $42.5 million. We are not obligated to make any additional milestone payments for any additional indications. Inaddition, we have agreed to pay AstraZeneca tiered royalties ranging from a high single-digit to mid-teens on net sales of any approved product based onINS1007 and one additional payment of $35.0 million upon the first achievement of $1 billion in annual net sales. The AZ License Agreement providesAstraZeneca with the option to negotiate a future agreement with us for commercialization of INS1007 in chronic obstructive pulmonary disease or asthma.In December 2014, we entered into a services agreement with SynteractHCR, Inc. (Synteract) pursuant to which we retained Synteract to performimplementation and management services in connection with the CONVERT study. We anticipate that aggregate costs relating to all work orders for theCONVERT study will be approximately $48 million over the period of the study. In April 2015, we entered into a work order with Synteract to performimplementation and management services for the completed 312 study.In 2004 and 2009, we entered into research funding agreements with Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT) whereby we received$1.7 million and $2.2 million for each respective agreement in research funding for the development of ARIKAYCE. If ARIKAYCE becomes an approvedproduct for certain infections in CF patients or such infections in human pulmonary disease in the US, we will owe a payment to CFFT of up to $13.4 millionthat is payable over a three-year period after regulatory approval in the US. Furthermore, if certain global sales milestones are met within five years of thedrug's commercialization, we would owe additional payments of $3.9 million. Because there is significant development and regulatory risk associated withARIKAYCE, including with respect to the CF indication, we have not accrued these obligations.Future Funding RequirementsWe may need to raise additional capital to fund our operations, including the continued commercialization of ARIKAYCE, future clinical trialsrelated to ARIKAYCE, development of INS1007 and INS1009, and the potential development, acquisition, in-license or co-promotion of other products orproduct candidates that address orphan or rare diseases. We expect that our future capital requirements may be substantial and will depend on many factors,including:•the timing and cost of our future clinical trials of ARIKAYCE for the treatment of patients with NTM lung infections;•the decisions of the EMA, MHLW and PMDA with respect to our applications for marketing approval of ARIKAYCE in Europe and Japan;•the costs of activities related to the regulatory approval process and the timing of approvals, if received;•the cost of supporting the sales and marketing efforts necessary to support the continued commercial efforts of ARIKAYCE;•the cost of filing, prosecuting, defending, and enforcing patent claims;•the timing and cost of our anticipated clinical trials, including INS1007 and the related milestone payments due to AstraZeneca;•the costs of our manufacturing-related activities;•the costs associated with commercializing ARIKAYCE outside the US, if approved; and•subject to receipt of marketing approval, the levels, timing and collection of revenue received from sales of approved products, if any, in the future.We have raised $813.5 million in net proceeds from securities offerings since September 2017. We believe we currently have sufficient funds to meetour financial needs for at least the next 12 months. However, our business strategy may require us to raise additional capital at any time through equity ordebt financing(s), strategic transactions or otherwise.Off-Balance Sheet ArrangementsWe do not have any off-balance sheet arrangements, other than operating leases, that have or are reasonably likely to have a current or futurematerial effect on our financial condition, revenues or expenses, results of operations, liquidity, capital expenditures or capital resources. We do not have anyinterest in special purpose entities, structured finance entities or other variable interest entities.CRITICAL ACCOUNTING POLICIES63Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsPreparation of financial statements in accordance with generally accepted accounting principles in the US requires us to make estimates andassumptions affecting the reported amounts of assets, liabilities, revenues and expenses and the disclosures of contingent assets and liabilities. We use ourhistorical experience and other relevant factors when developing our estimates and assumptions. We continually evaluate these estimates and assumptions.The amounts of assets and liabilities reported in our consolidated balance sheets and the amounts reported in our consolidated statements of comprehensiveloss are affected by estimates and assumptions, which are used for, but not limited to, the accounting for revenue recognition, research and development,stock-based compensation, inventory, identifiable intangible assets, and accrued expenses. The accounting policies discussed below are considered criticalto an understanding of our consolidated financial statements because their application involves the most significant judgment. Actual results could differmaterially from our estimates. For additional accounting policies, see Note 2 to our Consolidated Financial Statements—Summary of Significant AccountingPolicies.Revenue RecognitionIn accordance with Accounting Standards Codification 606, Revenue from Contracts with Customers (ASC 606), we recognize revenue when acustomer obtains control of promised goods or services, in an amount that reflects the consideration we expect to receive in exchange for the goods orservices provided. To determine revenue recognition for arrangements within the scope of ASC 606, we perform the following five steps: (1) identify thecontracts with a customer; (2) identify the performance obligations in the contract; (3) determine the transaction price; (4) allocate the transaction price to theperformance obligations in the contract; and (5) recognize revenue when or as the entity satisfies a performance obligation. At contract inception, we assessthe goods or services promised within each contract and determine those that are distinct performance obligations. We then recognize as revenue the amountof the transaction price that is allocated to the respective performance obligation when or as the performance obligation is satisfied. For all contracts that fallinto the scope of ASC 606, we have identified one performance obligation: the delivery of ARIKAYCE to our customers. We did not incur or capitalize anyincremental costs associated with obtaining contracts with customers.Product revenues consist primarily of sales of ARIKAYCE in the US. Product revenues are recognized once we perform all five steps mentionedabove. In October 2018, we began shipping ARIKAYCE to our customers in the US, which include specialty pharmacies and specialty distributors. Werecognize revenues for product received by our customers net of allowances for customer credits, including estimated rebates, chargebacks, prompt paydiscounts, returns, service fees, and government rebates, such as Medicaid rebates and Medicare Part D coverage gap reimbursements in the US. Customer credits: Our customers are offered various forms of consideration, including service fees and prompt payment discounts. We anticipatethat our customers will earn prompt payment discounts and, therefore, deduct the full amount of these discounts from total gross product revenues whenrevenues are recognized. Service fees are also deducted from total gross product revenues as they are earned. Rebates: We contract with Medicaid, other government agencies and various private organizations, or collectively, third-party payors, so thatARIKAYCE will be eligible for purchase by, or partial or full reimbursement from, such third-party payors. We estimate the rebates we will provide to third-party payors and deduct these estimated amounts from total gross product revenues at the time the revenues are recognized. Chargebacks: Chargebacks are discounts that occur when certain contracted customers, currently public health service institutions and federalgovernment entities purchasing via the Federal Supply Schedule, purchase directly from our specialty distributor. Contracted customers generally purchasethe product at a discounted price and the specialty distributor, in turn, charges back to us the difference between the price they initially paid and thediscounted price paid by the contracted customers. We estimate the chargebacks provided to the specialty distributor and deduct these estimated amountsfrom gross product revenues at the time revenues are recognized.Co-payment assistance: Patients who have commercial insurance and meet certain eligibility requirements may receive co-payment assistance. Weaccrue a liability for co-payment assistance based on actual program participation and estimates of program redemption using data provided by a third-partyadministrator.If any, or all, of our actual experience vary from the estimates above, we may need to adjust prior period accruals, affecting revenue in the period ofadjustment.In addition, upon US FDA approval of ARIKAYCE, we began recognizing revenue from sales under an ATU program in France. Pursuant to thisprogram, we ship product to pharmacies after receiving requests from physicians for patients in France. We are initiating expanded access programs (EAPs) inEurope and other countries, some of which may be64Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contentsfully reimbursed. EAPs are intended to make products available on a named patient basis before they are commercially available in accordance with localregulations.Research and DevelopmentR&D expenses consist of salaries, benefits and other related costs, including stock-based compensation, for personnel serving in our research anddevelopment functions, including medical affairs. Expenses also include other internal operating expenses, the cost of manufacturing our drugcandidate(s) for clinical study, the cost of conducting clinical studies, and the cost of conducting preclinical and research activities. In addition, our R&Dexpenses include payments to third parties for the license rights to products in development (prior to marketing approval), such as for INS1007. Our expensesrelated to manufacturing our drug candidate(s) for clinical study are primarily related to activities at CMOs that manufacture our product candidates for ouruse, including purchases of active pharmaceutical ingredients. Our expenses related to clinical trials are primarily related to activities at contract researchorganizations that conduct and manage clinical trials on our behalf.Since 2011, we have focused our development activities principally on our proprietary, advanced technologies designed specifically for inhaledtherapies. Our development efforts in 2018 and 2017 principally related to the development of ARIKAYCE in NTM lung disease.Stock-Based CompensationWe recognize stock-based compensation expense for awards of equity instruments to employees and directors based on the grant-date fair value ofthose awards. The grant-date fair value of the award is recognized as compensation expense ratably over the requisite service period, which generally equalsthe vesting period of the award, and if applicable, is adjusted for expected forfeitures. We also grant performance-based stock options to employees. Thegrant-date fair value of the performance-based stock options is recognized as compensation expense over the implicit service period using the acceleratedattribution method once it is probable that the performance condition will be achieved. Stock-based compensation expense is included in both R&Dexpenses and SG&A expenses in the consolidated statements of comprehensive loss.The following table summarizes the assumptions used in determining the fair value of stock options granted during the years ended December 31,2018, 2017 and 2016: 2018 2017 2016Volatility 66% - 68% 71% - 79% 74% - 77%Risk-free interest rate 2.25% - 2.96% 1.73% - 2.13% 1.00% - 1.90%Dividend yield 0.0% 0.0% 0.0%Expected option term (in years) 5.09 6.25 6.25For the years ended December 31, 2018, 2017 and 2016, the volatility factor was based on our historical volatility during the expected term orsince the closing of our merger with Transave, Inc. in December 2010. The risk-free interest rate is based on the US Treasury yield in effect at the date of grant.Estimated forfeitures were based on the actual percentage of option forfeitures since the closing of the Company’s merger with Transave, Inc. inDecember 2010 for the year ended December 31, 2016. Beginning with the year ended December 31, 2017, estimated forfeitures were based on the actualpercentage of option forfeitures over the expected option term.Accrued ExpensesWe are required to estimate accrued expenses as part of our process of preparing financial statements. This process involves estimating the level ofservice performed on our behalf and the associated cost incurred in instances where we have not been invoiced or otherwise notified of actual costs. Examplesof areas in which subjective judgments may be required include costs associated with services provided by contract organizations for preclinicaldevelopment, clinical trials and manufacturing of clinical materials. We accrue for expenses associated with these external services by determining the totalcost of a given study based on the terms of the related contract as the services are being provided by monitoring the status of the trials and the invoicesreceived from our external service providers. In the case of clinical trials, the estimated cost normally relates to the projected costs of having subjects enrolledin our trials, which we recognize over the estimated term of the trial according to the number of subjects enrolled in the trial on an ongoing basis, beginningwith subject enrollment. As actual costs become known to us, we adjust our accruals. To date, the number of clinical trials and related research serviceagreements has been relatively limited and our estimates have not differed significantly from the actual costs incurred.New Accounting Pronouncements—Adopted65Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsIn August 2016, the Financial Accounting Standards Board (FASB) issued Accounting Standard Update (ASU) 2016-15, Statement of Cash Flows(Topic 230): Classification of Certain Cash Receipts and Cash Payments, which addressed eight specific cash flow issues with the objective of reducing theexisting diversity in practice. Among the updates, the standard requires debt extinguishment costs to be classified as cash outflows for financing activities.This standard update became effective as of the first quarter of 2018. As a result of the adoption of the standard, in the first quarter of 2018, the Companyreported a $2.2 million loss on extinguishment of debt in the financing activities section of its consolidated statement of cash flows. The Company had nomaterial debt extinguishment costs prior to the first quarter of 2018. The impact of adopting this standard was not material to the Company.In May 2014, the FASB issued ASU 2014-09, Revenue from Contracts with Customers (Topic 606) which amended the then-existing accountingstandards for revenue recognition. ASU 2014-09 establishes principles for recognizing revenue upon the transfer of promised goods or services to customers,in an amount that reflects the expected consideration received in exchange for those goods or services. In July 2015, the FASB deferred the effective date forannual reporting periods beginning after December 15, 2017. We adopted ASU 2014-09 in the first quarter of 2018 and the impact of adopting the standardwas not material to our consolidated financial statements.Recent Accounting Pronouncements—Not Yet AdoptedIn February 2016, the FASB issued ASU 2016-02, Leases (Topic 842) in order to increase transparency and comparability among organizations byrecognizing lease assets and lease liabilities on the balance sheet for those leases classified as operating leases under previous generally accepted accountingprinciples. ASU 2016-02 requires a lessee to recognize a liability to make lease payments (the lease liability) and a right-of-use asset representing its right touse the underlying asset for the lease term on the balance sheet. ASU 2016-02 is effective for fiscal years beginning after December 15, 2018 (includinginterim periods within those periods) and early adoption is permitted. In August 2018, the FASB issued ASU 2018-11, Targeted Improvements to ASC 842,which provides a new transition option in which an entity initially applies ASU 2016-02 at the adoption date and recognizes a cumulative-effect adjustmentto the opening balance of retained earnings in the period of adoption. We will use the new transition option and will be also utilizing the package of practicalexpedients that allows it to not reassess: (1) whether any expired or existing contracts are or contain leases, (2) lease classification for any expired or existingleases, and (3) initial direct costs for any expired or existing leases. We will also use the short-term lease exception for leases with a term of twelve months orless. Additionally, we expect to use the practical expedient that allows us to treat the lease and non-lease components of our leases as a single component. Wehave identified approximately ten leasing arrangements and estimate the impact on our consolidated balance sheet to be approximately $44.0 million to$49.0 million. There will be no adjustment recognized through retained earnings as a result of adoption. We will adopt ASU 2016-02 effective January 1,2019, and we are continuing to evaluate the impact of adoption on our consolidated financial statements and our internal control over financial reporting.In June 2016, the FASB issued ASU 2016-13, Financial Instruments - Credit Losses which requires financial assets measured at an amortized costbasis to be presented at the net amount expected to be collected. The measurement of expected credit losses is based on relevant information about pastevents, including historical experience, current conditions, and reasonable and supportable forecasts that affect the collectability of the reported amount.ASU 2016-13 is effective for fiscal years effective for fiscal years after beginning after December 15, 2019. Different aspects of the guidance require modifiedretrospective or prospective adoption. We are currently evaluating the impact of adoption on our consolidated financial statements.ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISKAs of December 31, 2018, our cash and cash equivalents were in cash accounts or were invested in US treasury bills and money market funds. Ourinvestments in US treasury bills and money market funds are not insured by the federal government.As of December 31, 2018, we had $450.0 million of Convertible Notes outstanding which bear interest at a coupon rate of 1.75%. If a 10% changein interest rates had occurred on December 31, 2018, it would not have had a material effect on the fair value of our debt as of that date, nor would it have hada material effect on our future earnings or cash flows.The majority of our business is conducted in US dollars. However, we do conduct certain transactions in other currencies, including Euros, BritishPounds and Japanese Yen. Historically, fluctuations in foreign currency exchange rates have not materially affected our results of operations. During theyears ended December 31, 2018, 2017 and 2016, our results of operations were not materially affected by fluctuations in foreign currency exchange rates.ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA66Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsThe information required by Item 8 is included in our Financial Statements and Supplementary Data set forth in Item 15 of Part IV of this AnnualReport on Form 10-K.ITEM 9. CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND FINANCIAL DISCLOSURENone.ITEM 9A. CONTROLS AND PROCEDURESEvaluation of Disclosure Controls and ProceduresOur management, under the supervision and with the participation of our Chief Executive Officer and Chief Financial Officer, evaluated theeffectiveness of our disclosure controls and procedures as of December 31, 2018. The term "disclosure controls and procedures," as defined in Rules 13a-15(e)and 15d- 15(e) under the Securities Exchange Act of 1934, as amended (the Exchange Act) means controls and other procedures that are designed to providereasonable assurance that information required to be disclosed by us in the periodic reports that we file or submit with the SEC is recorded, processed,summarized and reported, within the time periods specified in the SEC's rules and forms, and to ensure that such information is accumulated andcommunicated to our management, including our Chief Executive Officer and Chief Financial Officer, as appropriate, to allow timely decisions regardingrequired disclosure. Based on that evaluation, as of December 31, 2018, our Chief Executive Officer and Chief Financial Officer have concluded that ourdisclosure controls and procedures were effective at the reasonable assurance level.Management's Report on Internal Control Over Financial ReportingOur management is responsible for establishing and maintaining adequate internal control over financial reporting. Internal control over financialreporting is defined in Rule 13a-15(f) and 15d-15(f) under the Exchange Act , as a process designed by, or under the supervision of, our principal executiveand principal financial and accounting officers and effected by our board of directors and management to provide reasonable assurance regarding thereliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accountingprinciples and includes those policies and procedures that:•Pertain to the maintenance of records that in reasonable detail accurately and fairly reflect the transactions and dispositions of our assets;•Provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance with USgenerally accepted accounting principles, and that receipts and expenditures of our company are being made only in accordance with authorizationsof our management and board of directors; and•Provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use or disposition of our assets that could have amaterial effect on the financial statements.Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Projections of any evaluationof effectiveness to future periods are subject to the risks that controls may become inadequate because of changes in conditions, or that the degree ofcompliance with the policies or procedures may deteriorate. Our management assessed the effectiveness of our internal control over financial reporting as ofDecember 31, 2018, based on the criteria set forth by the Committee of Sponsoring Organizations of the Treadway Commission (COSO) in Internal Control—Integrated Framework. A material weakness is a deficiency, or a combination of deficiencies, in internal control over financial reporting, such that there is areasonable possibility that a material misstatement of a company's annual or interim financial statements will not be prevented or detected on a timely basis.Based on management's assessment, management concluded that the Company's internal control over financial reporting was effective as of December 31,2018.Changes in Internal Control Over Financial ReportingDuring the year ended December 31, 2018, we implemented processes and internal controls to record product revenue, cost of product revenues, andinventory as a result of the FDA approval and the US commercial launch of ARIKAYCE. The implementation of these processes resulted in material changesto our internal controls over financial reporting. There were no other changes in our internal controls over financial reporting identified in connection withthe evaluation required by Rule 13a-15(d) and 15d-15(d) of the Exchange Act that occurred during the year ended December 31, 2018 that have materiallyaffected, or are reasonably likely to materially affect, our internal control over financial reporting.Attestation Report on Internal Control over Financial Reporting67Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsErnst & Young LLP, our independent registered public accounting firm, issued an attestation report on our internal control over financialreporting. The report of Ernst & Young LLP is contained in Item 15 of Part IV of this Annual Report on Form 10-K.ITEM 9B. OTHER INFORMATIONNone68Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsPART IIIITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCEThe information required by Item 10 of Form 10-K is incorporated by reference from the discussion responsive thereto under the captions Electionof Class I Directors, Corporate Governance and Section 16(a) Beneficial Ownership Reporting Compliance in our definitive proxy statement for our 2019annual meeting of shareholders to be filed with the SEC no later than 120 days after the close of the fiscal year covered by this Annual Report on Form 10-K.ITEM 11. EXECUTIVE COMPENSATIONThe information required by Item 11 of Form 10-K is incorporated by reference from the discussion responsive thereto under the captionsCompensation Discussion and Analysis, Compensation Committee Report, Compensation Committee Interlocks and Insider Participation and DirectorCompensation in our definitive proxy statement for our 2019 annual meeting of shareholders to be filed with the SEC no later than 120 days after the close ofthe fiscal year covered by this Annual Report on Form 10-K.ITEM 12. SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND RELATED STOCKHOLDER MATTERSThe information required by Item 12 of Form 10-K is incorporated by reference from the discussion responsive thereto under the captionsCompensation Discussion and Analysis, Security Ownership of Certain Beneficial Owners, Directors and Management in our definitive proxy statement forour 2019 annual meeting of shareholders to be filed with the SEC no later than 120 days after the close of the fiscal year covered by this Annual Report onForm 10-K.ITEM 13. CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS AND DIRECTOR INDEPENDENCEThe information required by Item 13 of Form 10-K is incorporated by reference from the discussion responsive thereto under the captions Electionof Class I Directors and Certain Relationships and Related Transactions in our definitive proxy statement for our 2019 annual meeting of shareholders to befiled with the SEC no later than 120 days after the close of the fiscal year covered by this Annual Report on Form 10-K.ITEM 14. PRINCIPAL ACCOUNTANT FEES AND SERVICESThe information required by Item 14 of Form 10-K is incorporated by reference from the discussion responsive thereto under the caption CorporateGovernance and Ratification of the Appointment of Independent Registered Public Accounting Firm in our definitive proxy statement for our 2019 annualmeeting of shareholders to be filed with the SEC no later than 120 days after the close of the fiscal year covered by this Annual Report on Form 10-K.69Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsPART IVITEM 15. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES(a)Documents filed as part of this report.1. FINANCIAL STATEMENTS. The following consolidated financial statements of the Company are set forth herein, beginning on page 76:(i)Reports of Independent Registered Public Accounting Firm(ii)Consolidated Balance Sheets as of December 31, 2018 and 2017(iii)Consolidated Statements of Comprehensive Loss for the Years Ended December 31, 2018, 2017 and 2016(iv)Consolidated Statements of Shareholders' Equity for the Years Ended December 31, 2018, 2017 and 2016(v)Consolidated Statements of Cash Flows for the Years Ended December 31, 2018, 2017 and 2016(vi)Notes to Consolidated Financial Statements2. FINANCIAL STATEMENT SCHEDULES.None required.3. EXHIBITS.The exhibits that are required to be filed or incorporated by reference herein are listed in the Exhibit Index.EXHIBIT INDEX3.1 Articles of Incorporation of Insmed Incorporated, as amended through June 14, 2012 (incorporated by reference fromExhibit 3.1 to Insmed Incorporated's Annual Report on Form 10-K filed on March 18, 2013 (SEC file no. 000-30739)). 3.2 Amended and Restated Bylaws of Insmed Incorporated (incorporated by reference from Exhibit 3.1 to InsmedIncorporated's Quarterly Report on Form 10-Q filed on August 6, 2015). 4.1 Specimen stock certificate representing common stock, $0.01 par value per share, of the Registrant (incorporated byreference from Exhibit 4.2 to Insmed Incorporated's Registration Statement on Form S-4/A (Registration No. 333-30098) filed on March 24, 2000). 4.2 Indenture, dated as of January 26, 2018, by and between the Company and Wells Fargo Bank, National Association(incorporated by reference from Exhibit 4.1 to Insmed Incorporated’s Current Report on Form 8-K filed on January26, 2018). 4.3 First Supplemental Indenture, dated as of January 26, 2018, by and between the Company and Wells Fargo Bank,National Association (incorporated by reference from Exhibit 4.2 to Insmed Incorporated’s Current Report on Form8-K filed on January 26, 2018). 4.4 Form of 1.75% Convertible Senior Note due 2025 (included in Exhibit 4.3). 10.1** Insmed Incorporated Amended and Restated 2000 Stock Incentive Plan (incorporated by reference from Exhibit 10.3to Insmed Incorporated's Form 10-Q filed on May 8, 2013 (SEC file no. 000-30739)). 10.2** Insmed Incorporated 2013 Incentive Plan (incorporated by reference from Exhibit 99.1 to Insmed Incorporated'sRegistration Statement on Form S-8 filed on May 24, 2013 (SEC file no. 333-188852)). 10.3** Insmed Incorporated 2015 Incentive Plan (incorporated by reference from Exhibit 99.1 to Insmed Incorporated'sRegistration Statement on Form S-8 filed on May 28, 2015). 10.4** Insmed Incorporated 2017 Incentive Plan (incorporated by reference from Exhibit 10.3 to Insmed Incorporated’sForm 10-Q filed August 3, 2017). 70Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contents10.5** Form of Award Agreement for Restricted Stock Units issued to employees pursuant to the Insmed Incorporated 2013Incentive Plan (incorporated by reference from Exhibit 10.3 to Insmed Incorporated's Form 10-K filed on March 6,2014). 10.6** Form of Award Agreement for Restricted Stock Units issued to directors pursuant to the Insmed Incorporated 2013Incentive Plan (incorporated by reference from Exhibit 10.4 to Insmed Incorporated's Form 10-K filed on March 6,2014). 10.7** Form of Award Agreement for Restricted Stock Units issued to directors pursuant to the Insmed Incorporated 2015Incentive Plan (incorporated by reference from Exhibit 10.1 to Insmed Incorporated’s Form 10-Q filed May 3, 2017). 10.8** Form of Restricted Unit Award Agreement under the Insmed Incorporated 2017 Incentive Plan (incorporated byreference from Exhibit 10.4 to Insmed Incorporated’s Form 10-Q filed August 3, 2017). 10.9** Form of Award Agreement for an Incentive Stock Option pursuant to the Insmed Incorporated 2013 Incentive Plan(incorporated by reference from Exhibit 10.5 to Insmed Incorporated's Form 10-K filed on March 6, 2014). 10.10** Form of Award Agreement for a Non-Qualified Stock Option pursuant to the Insmed Incorporated 2013 IncentivePlan (incorporated by reference from Exhibit 10.6 to Insmed Incorporated's Form 10-K filed on March 6, 2014). 10.11** Form of Award Agreement for a Non-Qualified Stock Option pursuant to the Insmed Incorporated 2015 IncentivePlan (incorporated by reference from Exhibit 10.2 to Insmed Incorporated’s Form 10-Q filed May 3, 2017). 10.12** Form of Non-Qualified Stock Option Agreement pursuant to the Insmed Incorporated 2017 Incentive Plan(incorporated by reference from Exhibit 10.5 to Insmed Incorporated’s Form 10-Q filed August 3, 2017). 10.13** Form of Non-Qualified Stock Option Inducement Award Agreement pursuant to the Insmed Incorporated 2017Incentive Plan (incorporated by reference from Exhibit 10.6 to Insmed Incorporated’s Form 10-Q filed August 3,2017). 10.14** Employment Agreement, effective as of September 10, 2012, between Insmed Incorporated and William Lewis(incorporated by reference from Exhibit 10.1 to Insmed Incorporated's Current Report on Form 8-K filed onSeptember 11, 2012). 10.15* License agreement, dated April 25, 2008, between Transave, Inc. and PARI Pharma GmbH, and Amendments No. 1-4thereto (incorporated by reference from Exhibit 10.22 to Insmed Incorporated's Annual Report on Form 10-K filed onMarch 18, 2013). 10.15.1* Amendment No. 5 to License Agreement between Insmed Incorporated and PARI Pharma GmbH, effective as ofOctober 5, 2015 (incorporated by reference from Exhibit 10.14.1 to Insmed Incorporated's Annual Report onForm 10-K filed on February 25, 2016). 10.15.2* Amendment No. 6 to License Agreement between Insmed Incorporated and PARI Pharma GmbH, effective as ofOctober 9, 2015 (incorporated by reference from Exhibit 10.14.2 to Insmed Incorporated's Annual Report onForm 10-K filed on February 25, 2016). 10.15.3* Amendment No. 7 to License Agreement between Insmed Incorporated and PARI Pharma GmbH, effective as of July21, 2017 (incorporated by reference from Exhibit 10.1 to Insmed Incorporated’s Form 10-Q filed on November 2,2017). 10.15.4* Amendment No. 8 to License Agreement between Insmed Incorporated and PARI Pharma GmbH, effective as ofDecember 19, 2018 (filed herewith). 10.16** Employment Agreement, effective as of July 29, 2013, between Insmed Incorporated and Christine Pellizzari(incorporated by reference from Exhibit 10.1 to Insmed Incorporated's Form 10-Q filed on November 5, 2013 (SECfile no. 000-30739)). 10.17** Insmed Incorporated Senior Executive Bonus Plan (incorporated by reference from Exhibit 10.2 to InsmedIncorporated's Form 10-Q filed on November 5, 2013). 10.18 Lease, dated December 31, 2013, between Denver Road, LLC and Insmed Incorporated (incorporated by referencefrom Exhibit 10.1 to Insmed Incorporated's Current Report on Form 8-K filed on January 3, 2014 (SEC file no. 000-30739)).71Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contents 10.18.1 First Amendment to Lease, dated April 29, 2014, between Denver Road, LLC and Insmed Incorporated (incorporatedby reference from Exhibit 10.17.1 to Insmed Incorporated's Annual Report on Form 10-K filed on February 25,2016). 10.18.2 Second Amendment to Lease, dated November 20, 2015, between Denver Road, LLC and Insmed Incorporated(incorporated by reference from Exhibit 10.17.2 to Insmed Incorporated's Annual Report on Form 10-K filed onFebruary 25, 2016). 10.19 Form of Indemnification Agreement entered into with each of the Company's directors and officers (incorporated byreference from Exhibit 10.1 to Insmed Incorporated's Current Report on Form 8-K filed on January 16, 2014 (SEC fileno. 000-30739)). 10.20* Contract Manufacturing Agreement, dated February 7, 2014, between Insmed Incorporated and TherapureBiopharma Inc. (incorporated by reference from Exhibit 10.1 to Insmed Incorporated's Form 10-Q filed on May 8,2014). 10.21* Amending Agreement, dated March 13, 2014, between Insmed Incorporated and Therapure Biopharma Inc.(incorporated by reference from Exhibit 10.2 to Insmed Incorporated's Form 10-Q filed on May 8, 2014). 10.22* Commercialization Agreement dated July 8, 2014 between Insmed Incorporated and PARI Pharma GmbH(incorporated by reference from Exhibit 10.1 to Insmed Incorporated's Form 10-Q filed on November 6, 2014). 10.22.1* Amendment No. 1 to Commercialization Agreement between Insmed Incorporated and PARI Pharma GmbH,effective as of July 21, 2017 (incorporated by reference from Exhibit 10.2 to Insmed Incorporated’s Form 10-Q filedon November 2, 2017). 10.25* Master Agreement for Services, dated as of August 27, 2014, by and between Insmed Incorporated andSynteractHCR, Inc. (incorporated by reference from Exhibit 10.29 to Insmed Incorporated's Form 10-K filed onFebruary 27, 2015). 10.26* Work Order 1, dated as of December 30, 2014, by and between Insmed Incorporated and SynteractHCR, Inc.(incorporated by reference from Exhibit 10.30 to Insmed Incorporated's Form 10-K filed on February 27, 2015). 10.27* Change in Scope 1 to Work Order 1, dated as of May 27, 2016, by and between Insmed Incorporated andSynteractHCR, Inc. (incorporated by reference from Exhibit 10.2 to Insmed Incorporated's Form 10-Q filed August 4,2016). 10.28** Employment Agreement, effective as of January 2, 2013, between Insmed Incorporated and S. Nicole Schaeffer(incorporated by reference from Exhibit 10.2 to Insmed Incorporated's Form 10-Q filed on May 7, 2015). 10.29* Commercial Fill/Finish Services Agreement between Insmed Incorporated and Ajinomoto Althea, Inc., dated as ofSeptember 15, 2015 (incorporated by reference from Exhibit 10.1 to Insmed Incorporated's Form 10-Q filedNovember 6, 2015). 10.29.1 Extension of Commercial Fill/Finish Services Agreement between Insmed Incorporated and Ajinomoto Althea, Inc.,dated as of November 30, 2016 (incorporated by reference from Exhibit 10.30 to Insmed Incorporated’s Form 10-Kfiled February 23, 2017). 10.29.2 Extension of Commercial Fill/Finish Services Agreement between Insmed Incorporated and Ajinomoto Althea, Inc.,dated as of December 18, 2018 (filed herewith). 10.30 Lease Agreement, effective as of July 1, 2016, by and between Insmed Incorporated and CIP II/AR BridgewaterHoldings, LLC (incorporated by reference from Exhibit 10.1 to Insmed Incorporated's Form 10-Q filed August 4,2016). 10.31** Employment Agreement, effective as of September 27, 2016, between Insmed Incorporated and Roger Adsett(incorporated by reference from Exhibit 10.2 to Insmed Incorporated's Form 10-Q filed November 3, 2016). 10.32* License Agreement, dated October 4, 2016, between Insmed Incorporated and AstraZeneca AB (incorporated byreference from Exhibit 10.29 to Insmed Incorporated’s Form 10-K filed February 23, 2017). 10.33 Amendment to Employment Agreement, effective as of September 26, 2016, between Insmed Incorporated andChristine Pellizzari (incorporated by reference from Exhibit 10.31 to Insmed Incorporated’s Form 10-K filedFebruary 23, 2017). 72Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of Contents10.34 Amendment to Employment Agreement, effective as of September 26, 2016, between Insmed Incorporated and S.Nicole Schaeffer (incorporated by reference from Exhibit 10.32 to Insmed Incorporated’s Form 10-K filed February23, 2017). 10.35 Employment Agreement, effective as of June 1, 2017, between Insmed Incorporated and Paolo Tombesi(incorporated by reference from Exhibit 10.1 to Insmed Incorporated’s Form 10-Q filed August 3, 2017). 10.36 Employment Agreement, effective as of June 1, 2017, between Insmed Incorporated and Paul D. Streck (incorporatedby reference from Exhibit 10.2 to Insmed Incorporated’s Form 10-Q filed August 3, 2017). 10.37* Manufacturing and Supply Agreement between Insmed Incorporated and Patheon UK Limited, dated as ofOctober 20, 2017 (incorporated by reference from Exhibit 10.39 to Insmed Incorporated's Form 10-K filed February23, 2018). 10.38* Technology Transfer Agreement between Insmed Incorporated and Patheon UK Limited, dated as of October 20,2017 (incorporated by reference from Exhibit 10.39 to Insmed Incorporated's Form 10-K filed February 23, 2018). 10.39 Lease Agreement, dated September 11, 2018, by and between Insmed Incorporated and Exeter 700 Route 202/206,LLC (incorporated by reference from Exhibit 10.1 to Insmed Incorporated’s Current Report on Form 8-K filed onSeptember 17, 2018). 21.1 Subsidiaries of Insmed Incorporated (filed herewith). 23.1 Consent of Ernst & Young LLP (filed herewith). 31.1 Certification of William H. Lewis, Chairman and Chief Executive Officer (Principal Executive Officer) of InsmedIncorporated, pursuant to Rules 13a-14(a) and 15d-14(a) promulgated under the Securities Exchange Act of 1934, asadopted pursuant to Section 302 of the Sarbanes Oxley Act of 2003 (filed herewith). 31.2 Certification of Paolo Tombesi, Chief Financial Officer (Principal Financial and Accounting Officer) of InsmedIncorporated, pursuant to Rules 13a-14(a) and 15d-14(a) promulgated under the Securities Exchange Act of 1934, asadopted pursuant to Section 302 of the Sarbanes Oxley Act of 2003 (filed herewith). 32.1 Certification of William H. Lewis, Chairman and Chief Executive Officer (Principal Executive Officer) of InsmedIncorporated, pursuant to 18 USC Section 1350, as adopted pursuant to Section 906 of the Sarbanes Oxley Act of2003 (filed herewith). 32.2 Certification of Paolo Tombesi, Chief Financial Officer (Principal Financial and Accounting Officer) of InsmedIncorporated, pursuant to 18 USC Section 1350, as adopted pursuant to Section 906 of the Sarbanes Oxley Act of2003 (filed herewith). *Confidential treatment has been granted for certain portions of this exhibit. The confidential portions of this exhibithave been omitted and filed separately with the Securities and Exchange Commission. **Management contract or compensatory plan or arrangement of the Company required to be filed as an exhibit.ITEM 16. FORM 10-K SUMMARYNot applicable.73Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsSIGNATURESPursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signedon its behalf by the undersigned, thereunto duly authorized on February 22, 2019. INSMED INCORPORATEDa Virginia corporation(Registrant) By:/s/ WILLIAM H. LEWIS William H. Lewis Chairman and Chief Executive Officer(Principal Executive Officer)Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following persons on behalf of theRegistrant and in the capacities indicated on February 22, 2019.Signature Title /s/ WILLIAM H. LEWIS Chairman and Chief Executive Officer(Principal Executive Officer)William H. Lewis /s/ PAOLO TOMBESI Chief Financial Officer(Principal Financial and Accounting Officer)Paolo Tombesi /s/ DONALD HAYDEN, JR. DirectorDonald Hayden, Jr. /s/ ALFRED F. ALTOMARI DirectorAlfred F. Altomari /s/ DAVID R. BRENNAN DirectorDavid R. Brennan /s/ STEINAR J. ENGELSEN, M.D. DirectorSteinar J. Engelsen, M.D. /s/ DAVID W.J. MCGIRR DirectorDavid W.J. McGirr /s/ ELIZABETH MCKEE ANDERSON DirectorElizabeth McKee Anderson /s/ MELVIN SHAROKY, M.D. DirectorMelvin Sharoky, M.D. /s/ LEO LEE DirectorLeo Lee 74Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsReport of Independent Registered Public Accounting FirmTo the Shareholders and the Board of Directors of Insmed IncorporatedOpinion on the Financial StatementsWe have audited the accompanying consolidated balance sheets of Insmed Incorporated (the Company) as of December 31, 2018 and 2017, the relatedconsolidated statements of comprehensive loss, shareholders' equity and cash flows for each of the three years in the period ended December 31, 2018, andthe related notes (collectively referred to as the “financial statements”). In our opinion, the financial statements present fairly, in all material respects, theconsolidated financial position of the Company at December 31, 2018 and 2017, and the consolidated results of its operations and its cash flows for each ofthe three years in the period ended December 31, 2018, in conformity with U.S. generally accepted accounting principles.We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the Company'sinternal control over financial reporting as of December 31, 2018, based on criteria established in Internal Control-Integrated Framework issued by theCommittee of Sponsoring Organizations of the Treadway Commission (2013 framework), and our report dated February 22, 2019 expressed an unqualifiedopinion thereon.Basis for OpinionThese financial statements are the responsibility of the Company's management. Our responsibility is to express an opinion on the Company’s financialstatements based on our audits. We are a public accounting firm registered with the PCAOB and are required to be independent with respect to the Companyin accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonableassurance about whether the financial statements are free of material misstatement, whether due to error or fraud. Our audits included performing proceduresto assess the risks of material misstatement of the financial statements, whether due to error or fraud, and performing procedures that respond to those risks.Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the financial statements. Our audits also includedevaluating the accounting principles used and significant estimates made by management, as well as evaluating the overall presentation of the financialstatements. We believe that our audits provide a reasonable basis for our opinion./s/ Ernst & Young LLP We have served as the Company’s auditor since at least 1999, but we are unable to determine the specific year.Iselin, New JerseyFebruary 22, 201975Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsReport of Independent Registered Public Accounting FirmTo the Shareholders and the Board of Directors of Insmed IncorporatedOpinion on Internal Control over Financial ReportingWe have audited Insmed Incorporated’s internal control over financial reporting as of December 31, 2018, based on criteria established in Internal Control -Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework) (the COSO criteria). In ouropinion, Insmed Incorporated (the Company) maintained, in all material respects, effective internal control over financial reporting as of December 31, 2018,based on the COSO criteria.We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the consolidatedbalance sheets of the Company as of December 31, 2018 and 2017, and the consolidated statements of comprehensive loss, shareholders' equity and cashflows for each of the three years in the period ended December 31, 2018 of the Company and our report dated February 22, 2019 expressed an unqualifiedopinion thereon.Basis for OpinionThe Company’s management is responsible for maintaining effective internal control over financial reporting and for its assessment of the effectiveness ofinternal control over financial reporting included in the accompanying Management's Report on Internal Control Over Financial Reporting. Ourresponsibility is to express an opinion on the Company’s internal control over financial reporting based on our audit. We are a public accounting firmregistered with the PCAOB and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and theapplicable rules and regulations of the Securities and Exchange Commission and the PCAOB.We conducted our audit in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonableassurance about whether effective internal control over financial reporting was maintained in all material respects.Our audit included obtaining an understanding of internal control over financial reporting, assessing the risk that a material weakness exists, testing andevaluating the design and operating effectiveness of internal control based on the assessed risk, and performing such other procedures as we considerednecessary in the circumstances. We believe that our audit provides a reasonable basis for our opinion.Definition and Limitations of Internal Control Over Financial ReportingA company’s internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability of financial reportingand the preparation of financial statements for external purposes in accordance with generally accepted accounting principles. A company’s internal controlover financial reporting includes those policies and procedures that (1) pertain to the maintenance of records that, in reasonable detail, accurately and fairlyreflect the transactions and dispositions of the assets of the company; (2) provide reasonable assurance that transactions are recorded as necessary to permitpreparation of financial statements in accordance with generally accepted accounting principles, and that receipts and expenditures of the company are beingmade only in accordance with authorizations of management and directors of the company; and (3) provide reasonable assurance regarding prevention ortimely detection of unauthorized acquisition, use, or disposition of the company’s assets that could have a material effect on the financial statements.Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also, projections of any evaluation ofeffectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of compliancewith the policies or procedures may deteriorate. /s/ Ernst & Young LLP Iselin, New JerseyFebruary 22, 201976Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDConsolidated Balance Sheets(in thousands, except par value and share data) As of December 31, 2018 2017Assets Current assets: Cash and cash equivalents $495,072 $381,165Accounts receivable 5,515 —Inventory 7,032 —Prepaid expenses and other current assets 11,327 8,279Total current assets 518,946 389,444 Intangibles, net 58,675 58,200Fixed assets, net 22,636 12,432Other assets 4,299 1,971Total assets $604,556 $462,047 Liabilities and shareholders' equity Current liabilities: Accounts payable $17,741 $14,671Accrued expenses 38,254 17,142Accrued compensation 22,208 12,197Other current liabilities 1,529 646Total current liabilities 79,732 44,656 Debt, long-term 316,558 55,567Other long-term liabilities — 765Total liabilities 396,290 100,988 Shareholders' equity: Common stock, $0.01 par value; 500,000,000 authorized shares, 77,307,521 and 76,610,508issued and outstanding shares at December 31, 2018 and December 31, 2017, respectively 773 766Additional paid-in capital 1,489,664 1,318,181Accumulated deficit (1,282,162) (957,885)Accumulated other comprehensive loss (9) (3)Total shareholders' equity 208,266 361,059Total liabilities and shareholders' equity $604,556 $462,047 See accompanying notes to consolidated financial statements77Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDConsolidated Statements of Comprehensive Loss(in thousands, except per share data) 2018 2017 2016Revenues: Product, net$9,835 $— $—Total revenues9,835 — — Costs and expenses: Cost of product revenues (excluding amortization of intangible assets)2,423 — —Research and development145,283 109,749 122,721Selling, general and administrative168,218 79,171 50,679Amortization of intangible assets1,249 — —Total costs and expenses317,173 188,920 173,400 Operating loss(307,338) (188,920) (173,400) Investment income10,341 1,624 604Interest expense(25,472) (5,925) (3,498)Loss on extinguishment of debt(2,209) — —Other income, net602 300 119Loss before income taxes(324,076) (192,921) (176,175) Provision (benefit) for income taxes201 (272) 98 Net loss$(324,277) $(192,649) $(176,273) Basic and diluted net loss per share$(4.22) $(2.89) $(2.85) Weighted average basic and diluted common shares outstanding76,889 66,576 61,892 Net loss$(324,277) $(192,649) $(176,273) Other comprehensive income (loss): Foreign currency translation (losses) gains(6) 62 (65)Total comprehensive loss$(324,283) $(192,587) $(176,338) See accompanying notes to audited consolidated financial statements78Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDConsolidated Statements of Shareholders' Equity(in thousands) Common Stock AdditionalPaid-inCapital AccumulatedDeficit AccumulatedOtherComprehensiveLoss TotalShares Amount Balance at January 1, 201661,814 $618 $900,043 $(588,963) $— $311,698Comprehensive loss: Net loss (176,273) (176,273)Other comprehensive loss (65) (65)Exercise of stock options162 2 1,082 1,084Issuance of common stock for vesting of RSUs44 —Stock compensation expense 18,039 18,039Balance at December 31, 201662,020 $620 $919,164 $(765,236) $(65) $154,483Comprehensive loss: Net loss (192,649) (192,649)Other comprehensive loss 62 62Exercise of stock options379 4 3,429 3,433Net proceeds from issuance of common stock14,123 141 377,515 377,656Issuance of common stock for vesting of RSUs89 1 1Stock compensation expense 18,073 18,073Balance at December 31, 201776,611 $766 $1,318,181 $(957,885) $(3) $361,059Comprehensive loss: Net loss (324,277) (324,277)Other comprehensive loss (6) (6)Exercise of stock options and ESPP shares645 6 8,809 8,815Equity component of convertible debt issuance 136,434 136,434Issuance of common stock for vesting of RSUs52 1 1Stock compensation expense 26,240 26,240Balance at December 31, 201877,308 $773 $1,489,664 $(1,282,162) $(9) $208,266 See accompanying notes to audited consolidated financial statements79Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDConsolidated Statements of Cash Flows(in thousands) Years ended December 31, 201820172016Operating activities Net loss$(324,277) $(192,649) $(176,273)Adjustments to reconcile net loss to net cash used in operatingactivities: Depreciation3,577 2,901 2,438Amortization of intangible assets1,249 — —Stock-based compensation expense26,240 18,073 18,039Loss on extinguishment of debt2,209 — —Amortization of debt issuance costs1,350 118 281Accretion of debt discount15,889 — Accretion of back-end fee on debt50 658 171Changes in operating assets and liabilities: Accounts receivable(5,515) — —Inventory(7,032) — —Prepaid expenses and other assets(5,514) (2,783) 191Accounts payable3,870 3,604 2,767Accrued expenses and other19,916 5,201 3,043Accrued compensation10,011 5,260 2,635Net cash used in operating activities(257,977) (159,617) (146,708)Investing activities Purchase of fixed assets(13,090) (3,001) (4,200)PARI milestone upon FDA approval(1,724) — —Net cash used in investing activities(14,814) (3,001) (4,200)Financing activities Proceeds from issuance of 1.75% convertible senior notes due 2025450,000 — —Payment on extinguishment of debt(2,835) — —Payment of debt(55,000) — —Proceeds from issuance of debt— — 30,000Proceeds from issuance of common stock, net — 377,656 —Proceeds from exercise of stock options and ESPP8,815 3,433 1,084Payment of debt issuance costs(14,237) — (411)Net cash provided by financing activities 386,743 381,089 30,673Effect of exchange rates on cash and cash equivalents(45) 103 (50)Net increase (decrease) in cash and cash equivalents113,907 218,574 (120,285)Cash and cash equivalents at beginning of period381,165 162,591 282,876Cash and cash equivalents at end of period$495,072 $381,165 $162,591Supplemental disclosures of cash flow information: Cash paid for interest$6,289 $5,165 $3,608Cash paid for taxes, net$154 $166 $85 See accompanying notes to audited consolidated financial statements80Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS1. Description of Business and Basis of PresentationDescription of Business—Insmed is a global biopharmaceutical company on a mission to transform the lives of patients with serious and rarediseases. The Company's first commercial product, ARIKAYCE (amikacin liposome inhalation suspension), received accelerated approval in the UnitedStates (US) on September 28, 2018 for the treatment of refractory Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterialdrug regimen for adult patients with limited or no alternative treatment options. MAC lung disease is a rare and often chronic infection that can causeirreversible lung damage and can be fatal. The Company's clinical-stage pipeline includes INS1007 and INS1009. INS1007 is a novel oral, reversibleinhibitor of dipeptidyl peptidase 1 (DPP1) with therapeutic potential in non-cystic fibrosis (non-CF) bronchiectasis and other inflammatory diseases.INS1009 is an inhaled formulation of a treprostinil prodrug that may offer a differentiated product profile for rare pulmonary disorders, including pulmonaryarterial hypertension (PAH).The Company was incorporated in the Commonwealth of Virginia on November 29, 1999 and its principal executive offices are located inBridgewater, New Jersey. The Company has legal entities in the US, Ireland, Germany, France, the United Kingdom (UK), the Netherlands, Bermuda andJapan.The Company had $495.1 million in cash and cash equivalents as of December 31, 2018 and reported a net loss of $324.3 million for the year endedDecember 31, 2018. Historically, the Company has funded its operations through public offerings of equity securities and debt financings. To date, theCompany has not generated significant revenue from ARIKAYCE. The Company commenced commercial shipments in October 2018. The Company expectsto continue to incur operating losses while funding commercial launch efforts for ARIKAYCE, research and development (R&D) activities, regulatorysubmissions outside the US, and selling, general and administrative (SG&A) expenses. The Company expects its future cash requirements to be substantial,and it may need to raise additional capital to fund operations, including the commercialization of ARIKAYCE and additional clinical trials related toARIKAYCE, to develop INS1007 and INS1009 and to develop, acquire, in-license or co-promote other products that address orphan or rare diseases.The source, timing and availability of any future financing or other transaction will depend principally upon continued progress in the Company’scommercial, regulatory and development activities. Any equity or debt financing will also be contingent upon equity and debt market conditions andinterest rates at the time. If the Company is unable to obtain sufficient additional funds when required, the Company may be forced to delay, restrict oreliminate all or a portion of its development programs or commercialization efforts. The Company believes it currently has sufficient funds to meet itsfinancial needs for at least the next 12 months.Basis of Presentation—The consolidated financial statements include the accounts of the Company and its wholly-owned subsidiaries, InsmedLimited, Celtrix Pharmaceuticals, Inc., Insmed Holdings Limited, Insmed Ireland Limited, Insmed France SAS, Insmed Germany GmbH, InsmedNetherlands B.V., Insmed Bermuda Limited and Insmed Godo Kaisha. All intercompany transactions and balances have been eliminated in consolidation andcertain prior year amounts have been restated to conform to the current year presentation. In the prior year, accrued compensation was presented within theaccrued expense line in the consolidated balance sheet. In the current year, accrued compensation is presented as a discrete line on the face of theconsolidated balance sheet.2. Summary of Significant Accounting PoliciesUse of Estimates—The preparation of the consolidated financial statements in conformity with accounting principles generally accepted in theUnited States (GAAP) requires management to make estimates and assumptions that affect the amounts reported in the consolidated financial statements andaccompanying notes. The Company bases its estimates and judgments on historical experience and on various other assumptions. The amounts of assets andliabilities reported in the Company's balance sheets and the amounts of revenues and expenses reported for each period presented are affected by estimatesand assumptions, which are used for, but not limited to, the accounting for revenue allowances, stock-based compensation, income taxes, loss contingencies,and accounting for research and development costs. Actual results could differ from those estimates.Investment Income and Interest Expense—Investment income consists of interest income earned on the Company's cash and cash equivalents.Interest expense consists primarily of interest costs related to the Company's debt.Cash and Cash Equivalents—The Company considers cash equivalents to be highly liquid investments with maturities of three months or lessfrom the date of purchase.81Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)2. Summary of Significant Accounting Policies (Continued)Fixed Assets, Net—Fixed assets are recorded at cost and are depreciated on a straight-line basis over the estimated useful lives of the assets.Estimated useful lives of three years to five years are used for computer equipment. Estimated useful lives of seven years are used for laboratory equipment,office equipment, manufacturing equipment and furniture and fixtures. Leasehold improvements are amortized over the shorter of the lease term or theestimated useful life of the asset. Long-lived assets are reviewed for impairment whenever events or changes in circumstances indicate that the carryingamount of an asset may not be recoverable. Recoverability of assets to be held and used is measured by a comparison of the carrying amount of an asset toestimated undiscounted future cash flows expected to be generated by the asset. If the carrying amount of an asset exceeds its estimated future cash flows,then an impairment charge is recognized for the amount by which the carrying value of the asset exceeds the fair value of the asset.Identifiable Intangible Assets—Identifiable intangible assets are measured at their respective fair values and began amortizing over their estimateduseful lives upon commercialization. The fair values assigned to the Company's intangible assets are based on reasonable estimates and assumptions givenavailable facts and circumstances. Unanticipated events or circumstances may occur that may require the Company to review the assets for impairment.Events or circumstances that may require an impairment assessment include negative clinical trial results, the non-approval of a new drug application by aregulatory agency, material delays in the Company's development program or a sustained decline in market capitalization. The Company performs its annualimpairment test as of October 1 of each year.The Company performed a qualitative assessment to evaluate whether there was an impairment of the assets. This assessment did not identify anyindicators of impairment of the intangible assets as of that date.Debt Issuance Costs—Debt issuance costs are amortized to interest expense using the effective interest rate method over the term of the debt. Debtissuance costs paid to the lender and third parties are reflected as a discount to the debt in the consolidated balance sheets. Unamortized debt issuance costsassociated with extinguished debt are expensed in the period of the extinguishment.Fair Value Measurements—The Company categorizes its financial assets and liabilities measured and reported at fair value in the financialstatements on a recurring basis based upon the level of judgment associated with the inputs used to measure their fair value. Hierarchical levels, which aredirectly related to the amount of subjectivity associated with the inputs used to determine the fair value of financial assets and liabilities, are as follows:•Level 1 — Inputs are unadjusted, quoted prices in active markets for identical assets or liabilities at the measurement date. •Level 2 — Inputs (other than quoted prices included in Level 1) are either directly or indirectly observable for the assets or liability throughcorrelation with market data at the measurement date and for the duration of the instrument’s anticipated life. •Level 3 — Inputs reflect management’s best estimate of what market participants would use in pricing the asset or liability at the measurementdate. Consideration is given to the risk inherent in the valuation technique and the risk inherent in the inputs to the model. Each major category of financial assets and liabilities measured at fair value on a recurring basis is categorized based upon the lowest level ofsignificant input to the valuations. The fair value hierarchy also requires an entity to maximize the use of observable inputs and minimize the use ofunobservable inputs when measuring fair value. Financial instruments in Level 1 generally include US treasuries and mutual funds listed in active markets.The Company's only financial assets and liabilities which were measured at fair value as of December 31, 2018 and December 31, 2017 were Level1 assets comprised of cash and cash equivalents. The Company's cash and cash equivalents permit daily redemption and the fair values of these investmentsare based upon the quoted prices in active markets provided by the holding financial institutions. The following table shows assets and liabilities that aremeasured at fair value on a recurring basis and their carrying value (in millions):82Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)2. Summary of Significant Accounting Policies (Continued) As of December 31, 2018 Fair Value Carrying Value Level 1 Level 2 Level 3Cash and cash equivalents$495.1 $495.1 $— $— As of December 31, 2017 Fair Value Carrying Value Level 1 Level 2 Level 3Cash and cash equivalents$381.2 $381.2 $— $— The Company recognizes transfers between levels within the fair value hierarchy, if any, at the end of each quarter. There were no transfers in or out ofLevel 1, Level 2 or Level 3 during 2018 and 2017.As of December 31, 2018 and 2017, the Company held no securities that were in an unrealized loss or gain position.The Company reviews the status of each security quarterly to determine whether an other-than-temporary impairment has occurred. In making itsdetermination, the Company considers a number of factors, including: (1) the significance of the decline; (2) whether the security was rated below investmentgrade; (3) how long the security has been in an unrealized loss position; and (4) the Company's ability and intent to retain the investment for a sufficientperiod of time for it to recover.The estimated fair value of the liability component of the 1.75% convertible senior notes due 2025 (the Convertible Notes) (categorized as a Level 2liability for fair value measurement purposes) as of December 31, 2018 was $313.0 million, determined using current market factors and the ability of theCompany to obtain debt on comparable terms to the Convertible Notes. The $316.6 million carrying value of the Convertible Notes as of December 31, 2018excludes the $125.0 million of the unamortized portion of the debt discount.Foreign Currency—The Company has operations in the US, Ireland, Germany, France, the UK, the Netherlands and Japan. The results of its non-US dollar based functional currency operations are translated to US dollars at the average exchange rates during the period. Assets and liabilities aretranslated at the exchange rate prevailing at the balance sheet date. Equity is translated at the prevailing exchange rate at the date of the equity transaction.Translation adjustments are included in shareholders' equity, as a component of other comprehensive loss.The Company realizes foreign currency transaction gains (losses) in the normal course of business based on movements in the applicable exchangerates. These gains (losses) are included as a component of other income, net.Concentration of Credit Risk—Financial instruments that potentially subject the Company to concentrations of credit risk consist primarily ofcash and cash equivalents. The Company places its cash equivalents with high credit-quality financial institutions and may invest its short-term investmentsin US treasury securities, mutual funds and government agency bonds. The Company has established guidelines relative to credit ratings and maturities thatseek to maintain safety and liquidity.The Company is exposed to risks associated with extending credit to customers related to the sale of products. The Company does not requirecollateral to secure amounts due from its customers. The following table presents the percentage of gross product revenue represented by the Company's threelargest customers as of the year ended December 31, 2018. Percentage of Total GrossProduct RevenueCustomer A37%Customer B27%Customer C19%83Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)2. Summary of Significant Accounting Policies (Continued)The Company did not have product revenue prior to US FDA approval of ARIKAYCE in 2018. The Company relies on third-party manufacturersand suppliers for manufacturing and supply of its products. The inability of the suppliers or manufacturers to fulfill supply requirements of the Companycould materially impact future operating results. A change in the relationship with the suppliers or manufacturer, or an adverse change in their business, couldmaterially impact future operating results.Revenue Recognition—In accordance with ASC 606, Revenue from Contracts with Customers, the Company recognizes revenue when a customerobtains control of promised goods or services, in an amount that reflects the consideration the Company expects to receive in exchange for the goods orservices provided. To determine revenue recognition for arrangements within the scope of ASC 606, the Company performs the following five steps: (1)identify the contracts with a customer; (2) identify the performance obligations in the contract; (3) determine the transaction price; (4) allocate the transactionprice to the performance obligations in the contract; and (5) recognize revenue when or as the entity satisfies a performance obligation. At contract inception,the Company assesses the goods or services promised within each contract and determines those that are performance obligations and assesses whether eachpromised good or service is distinct. The Company then recognizes as revenue the amount of the transaction price that is allocated to the respectiveperformance obligation when or as the performance obligation is satisfied. For all contracts that fall into the scope of ASC 606, the Company has identifiedone performance obligation: the sale of ARIKAYCE to its customers. The Company did not incur or capitalize any incremental costs associated withobtaining contracts with customers.Product revenues consist primarily of sales of ARIKAYCE in the US. Product revenues are recognized once the Company performs and satisfies allfive steps mentioned above. In October 2018, the Company began shipping ARIKAYCE to its customers in the US, which include specialty pharmacies andspecialty distributors. The Company recognizes revenues for product received by its customers net of allowances for customer credits, including estimatedrebates, chargebacks, prompt pay discounts, returns, service fees, and government rebates, such as Medicaid rebates and Medicare Part D coverage gapreimbursements in the US. Customer credits: The Company’s customers are offered various forms of consideration, including service fees and prompt payment discounts. TheCompany anticipates that its customers will earn prompt payment discounts and, therefore, deducts the full amount of these discounts from total grossproduct revenues when revenues are recognized. Service fees are also deducted from total gross product revenues as they are earned. Rebates: The Company contracts with Medicaid, other government agencies and various private organizations, or collectively, third-party payors,so that ARIKAYCE will be eligible for purchase by, or partial or full reimbursement from, such third-party payors. The Company estimates the rebates it willprovide to third-party payors and deducts these estimated amounts from total gross product revenues at the time the revenues are recognized. Chargebacks: Chargebacks are discounts that occur when certain contracted customers, currently public health service institutions and federalgovernment entities purchasing via the Federal Supply Schedule, purchase directly from the Company's specialty distributor. Contracted customers generallypurchase the product at a discounted price and the specialty distributor, in turn, charges back to the Company the difference between the price initially paidby the specialty distributor and the discounted price paid by the contracted customers. The Company estimates the chargebacks it provides to the specialtydistributor and deducts these estimated amounts from total gross product revenues at the time the revenues are recognized.Co-payment assistance: Patients who have commercial insurance and meet certain eligibility requirements may receive co-payment assistance. TheCompany accrues a liability for co-payment assistance based on actual program participation and estimates of program redemption using data provided by athird-party administrator.If any, or all, of the Company’s actual experience vary from the estimates above, the Company may need to adjust prior period accruals, affectingrevenue in the period of adjustment.The following table provides a summary roll-forward of our sales allowances and related accruals for the year ended December 31, 2018 (inthousands), which have been deducted in arriving at net product revenue:84Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)2. Summary of Significant Accounting Policies (Continued) Customer fees, discountsand other Rebates, chargebacks andco-pay assistance TotalBalance as of January 1, 2018$— $— $— Allowances for current period sales335 849 1,184 Payments and credits(101) (161) (262)Balance as of December 31, 2018$234 $688 $922In addition, upon US FDA approval of ARIKAYCE, the Company began recognizing revenue from sales to the French National Agency forMedicines and Health Products Safety (ANSM), which granted ARIKAYCE a Temporary Authorizations for Use (Autorisation Temporaire d'Utilisation orATU). Pursuant to this program, the Company ships product to pharmacies after receiving requests from physicians for patients in France. The Company isinitiating expanded access programs (EAPs) in Europe and other countries, some of which may be fully reimbursed. EAPs are intended to make productsavailable on a named patient basis before they are commercially available in accordance with local regulations.Inventory and cost of product revenues (excluding amortization of intangible assets)—Inventory is stated at the lower of cost and net realizablevalue with cost determined on a standard costing method. The Company capitalized inventory costs following regulatory approval of ARIKAYCE from theFDA on September 28, 2018. Inventory is sold on a first-in, first out basis. Manufacturing variances, such as material usage variance and yield variance, arecapitalized in inventory until the respective units are sold, at which point the variances are recognized in cost of product revenues. The Companyperiodically reviews inventory for expiry and obsolescence and, if necessary, records a write-down accordingly. The Company also performs strict qualitycontrol throughout the manufacturing processes of products; however, certain batches or units of product may not meet quality specifications and result in acharge to cost of product revenues in the period incurred.Prior to FDA approval of ARIKAYCE, the Company expensed all inventory related costs in the period incurred; therefore, inventory is not includedin the December 31, 2017 consolidated balance sheet. Inventory that is used for clinical development purposes is expensed to research and developmentexpense when consumed.Cost of product revenues (excluding amortization of intangible assets) consist primarily of direct and indirect costs related to the manufacturing ofARIKAYCE sold, including third-party manufacturing costs, packaging services, freight-in, allocation of overhead costs, and inventory adjustment charges,in addition to royalty expenses due to PARI.Research and Development—Research and development expenses consist primarily of salaries, benefits and other related costs, including stock-based compensation, for personnel serving in the Company's research and development functions, and other internal operating expenses, the cost ofmanufacturing a drug candidate, including the medical devices for drug delivery, for clinical study, the cost of conducting clinical studies, and the cost ofconducting preclinical and research activities. In addition, research and development expenses include payments to third parties for the license rights toproducts in development (prior to marketing approval). The Company's expenses related to manufacturing its drug candidate and medical devices for clinicalstudy are primarily related to activities at contract manufacturing organizations that manufacture ARIKAYCE, INS1007, and INS1009 and the medicaldevices for the Company's use. The Company's expenses related to clinical trials are primarily related to activities at contract research organizations thatconduct and manage clinical trials on the Company's behalf. These contracts set forth the scope of work to be completed at a fixed fee or amount per patientenrolled. Payments under these contracts primarily depend on performance criteria such as the successful enrollment of patients or the completion of clinicaltrial milestones as well as time-based fees. Expenses are accrued based on contracted amounts applied to the level of patient enrollment and to activityaccording to the clinical trial protocol. Nonrefundable advance payments for goods or services that will be used or rendered for future research anddevelopment activities are deferred and capitalized. Such amounts are then recognized as an expense as the related goods are delivered or the services areperformed, or when the goods or services are no longer expected to be provided.Stock-Based Compensation—The Company recognizes stock-based compensation expense for awards of equity instruments to employees anddirectors based on the grant-date fair value of those awards. The grant-date fair value of the award is recognized as compensation expense ratably over therequisite service period, which generally equals the vesting period of the award, and if applicable, is adjusted for expected forfeitures. The Company alsogrants performance-based stock options to employees. The grant-date fair value of the performance-based stock options is recognized as compensationexpense over the implicit service period using the accelerated attribution method once it is probable that the performance condition will85Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)2. Summary of Significant Accounting Policies (Continued)be achieved. Stock-based compensation expense is included in both R&D and SG&A expenses in the consolidated statements of comprehensive loss.Income Taxes—The Company accounts for income taxes under the asset and liability method. Deferred tax assets and liabilities are recognized forthe future tax consequences attributable to differences between the financial statement carrying amounts of existing assets and liabilities and their respectivetax bases and operating loss carry forwards. Deferred tax assets and liabilities are measured using enacted tax rates expected to apply to taxable income in theyears in which those temporary differences are expected to be recovered or settled. The effect on deferred tax assets and liabilities of a change in tax rates isrecognized in income in the period that includes the enactment date.A valuation allowance is recorded to reduce the deferred tax assets to the amount that is expected to be realized. In evaluating the need for avaluation allowance, the Company takes into account various factors, including the expected level of future taxable income and available tax planningstrategies. If actual results differ from the assumptions made in the evaluation of a valuation allowance, the Company records a change in valuationallowance through income tax expense in the period such determination is made.The Company may recognize the tax benefit from an uncertain tax position only if it is more likely than not that the tax position will be sustainedon examination by taxing authorities, based solely on the technical merits of the position. The tax benefits recognized in the financial statements from such aposition should be measured based on the largest benefit that has a greater than 50% likelihood to be sustained upon ultimate settlement. As any adjustmentto the Company’s uncertain tax positions would not result in a cash tax liability, it has not recorded any accrued interest or penalties related to its uncertaintax positions.The Company's policy for interest and penalties related to income tax exposures is to recognize interest and penalties as a component of the incometax provision (benefit) in the consolidated statements of comprehensive loss.Net Loss Per Share—Basic net loss per share is computed by dividing net loss attributable to common shareholders by the weighted average numberof common shares outstanding during the period. Diluted net loss per share is computed by dividing net loss by the weighted average number of commonshares and other dilutive securities outstanding during the period. Potentially dilutive securities from stock options and restricted stock units would be anti-dilutive as the Company incurred a net loss in all periods presented. Potentially dilutive common shares resulting from the assumed exercise of outstandingstock options would be determined based on the treasury stock method.The following table sets forth the reconciliation of the weighted average number of shares used to compute basic and diluted net loss per share forthe years ended December 31, 2018, 2017 and 2016. Years Ended December 31,2018 2017 2016(in thousands, except per share amounts)Numerator: Net loss$(324,277) $(192,649) $(176,273)Denominator: Weighted average common shares used in calculation of basic net loss per share:76,889 66,576 61,892Effect of dilutive securities: Common stock options— — —Restricted stock and restricted stock units — — —Weighted average common shares outstanding used in calculation of diluted net loss pershare76,889 66,576 61,892Net loss per share: Basic and diluted$(4.22) $(2.89) $(2.85)86Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)2. Summary of Significant Accounting Policies (Continued)The following potentially dilutive securities have been excluded from the computations of diluted weighted average common shares outstandingas of December 31, 2018, 2017 and 2016 as their effect would have been anti-dilutive (in thousands). 2018 2017 2016Stock options to purchase common stock9,382 8,609 7,117Unvested restricted stock units228 47 89Convertible debt securities11,492 — —Segment Information—The Company currently operates in one business segment, which is the development and commercialization of therapiesfor patients with rare diseases. A single management team that reports to the Chief Executive Officer comprehensively manages the entire business. TheCompany does not operate separate lines of business with respect to its products or product candidates. Accordingly, the Company has one reportablesegment.New Accounting Pronouncements (Adopted)—In August 2016, the Financial Accounting Standards Board (FASB) issued Accounting StandardUpdate (ASU) 2016-15, Statement of Cash Flows (Topic 230): Classification of Certain Cash Receipts and Cash Payments, which addressed eight specificcash flow issues with the objective of reducing the existing diversity in practice. Among the updates, the standard requires debt extinguishment costs to beclassified as cash outflows for financing activities. This standard update became effective as of the first quarter of 2018. As a result of the adoption of thestandard, in the first quarter of 2018, the Company reported a $2.2 million loss on extinguishment of debt in the operating activities section of itsconsolidated statement of cash flows. The Company had no material debt extinguishment costs prior to the first quarter of 2018. The impact of adopting thisstandard was not material to the Company.In May 2014, the FASB issued ASU 2014-09, Revenue from Contracts with Customers (Topic 606) which amended the existing accountingstandards for revenue recognition. ASU 2014-09 establishes principles for recognizing revenue upon the transfer of promised goods or services to customers,in an amount that reflects the expected consideration received in exchange for those goods or services. In July 2015, the FASB deferred the effective date forannual reporting periods beginning after December 15, 2017. The Company adopted ASU 2014-09 in the first quarter of 2018. The adoption did not have amaterial impact on the Company's consolidated financial statements.New Accounting Pronouncements (Not Yet Adopted)—In February 2016, the FASB issued ASU 2016-02, Leases (Topic 842) in order to increasetransparency and comparability among organizations by recognizing lease assets and lease liabilities on the balance sheet for those leases classified asoperating leases under previous generally accepted accounting principles. ASU 2016-02 requires a lessee to recognize a liability to make lease payments (thelease liability) and a right-of-use asset representing its right to use the underlying asset for the lease term on the balance sheet. ASU 2016-02 is effective forfiscal years beginning after December 15, 2018 (including interim periods within those periods) and early adoption is permitted. In August 2018, the FASBissued ASU 2018-11, Targeted Improvements to ASC 842, which provides a new transition option in which an entity initially applies ASU 2016-02 at theadoption date and recognizes a cumulative-effect adjustment to the opening balance of retained earnings in the period of adoption. The Company will usethe new transition option and will be also utilizing the package of practical expedients that allows it to not reassess: (1) whether any expired or existingcontracts are or contain leases, (2) lease classification for any expired or existing leases, and (3) initial direct costs for any expired or existing leases. TheCompany will also use the short-term lease exception for leases with a term of twelve months or less. Additionally, the Company expects to use the practicalexpedient that allows it to treat the lease and non-lease components of its leases as a single component. The Company has identified approximately tenleasing arrangements and estimates the impact on its consolidated balance sheet to be approximately $44 million to $49 million. There will be no adjustmentrecognized through retained earnings as a result of adoption. The Company will adopt ASU 2016-02 effective January 1, 2019, and is continuing to evaluatethe impact of adoption on its consolidated financial statements and its internal control over financial reporting.In June 2016, the FASB issued ASU 2016-13, Financial Instruments - Credit Losses which requires financial assets measured at an amortized costbasis to be presented at the net amount expected to be collected. The measurement of expected credit losses is based on relevant information about pastevents, including historical experience, current conditions, and reasonable and supportable forecasts that affect the collectability of the reported amount.ASU 2016-13 is effective for fiscal years effective for fiscal years after beginning after December 15, 2019. Different aspects of the guidance require modified87Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)2. Summary of Significant Accounting Policies (Continued)retrospective or prospective adoption. The Company is currently evaluating the impact of adoption on its consolidated financial statements.3. InventoryAs of December 31, 2018, the Company's inventory balance consists of the following (in thousands): As of December 31,2018Raw materials$2,145Work-in-process4,567Finished goods320 $7,032Inventory is stated at the lower of cost or net realizable value and consists of raw materials, work-in-process and finished goods. Cost is determinedusing a standard cost method, which approximates actual cost, and assumes a FIFO flow of goods. The Company began capitalizing inventory costsfollowing FDA approval of ARIKAYCE on September 28, 2018. The Company has not recorded any inventory write downs since that time. The Companycurrently uses a limited number of third-party contract manufacturing organizations (CMOs) to produce its inventory.4. Accrued ExpensesAccrued expenses consist of the following: As of December 31,2018 2017(in thousands)Accrued clinical trial expenses$6,635 $7,837Accrued professional fees13,398 4,500Accrued technical operation expenses9,371 2,182Accrued interest payable3,631 423Accrued sales allowances and related costs818 —Accrued construction costs2,946 1,719Other accrued expenses1,455 481 $38,254 $17,1425. Intangibles, netAs of December 31, 2018, the Company's identifiable intangible assets consisted of acquired ARIKAYCE R&D, formerly referred to as in-processresearch and development, and a milestone paid to PARI Pharma GmbH (PARI) for the license to use PARI's Lamira® Nebulizer System for the delivery ofARIKAYCE to patients. The Company's only identifiable intangible asset was in-process research and development (IPRD) related to ARIKAYCE as ofDecember 31, 2017, which resulted from the initial amount recorded at the time of the Company's merger with Transave in 2010 and subsequent adjustmentsin the value. On September 28, 2018, as a result of the FDA approval of ARIKAYCE, the Company recorded a milestone payment of $1.7 million due toPARI. Total intangible assets, net was $58.7 million and $58.2 million as of December 31, 2018 and 2017, respectively.Intangible assets are measured at their respective fair values on the date they were recorded and, with respect to the Acquired ARIKAYCE milestone,at the date of subsequent adjustments of fair value. The Company began amortizing its88Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)5. Intangibles, net (Continued)intangible assets October 1, 2018, over ARIKAYCE's initial regulatory exclusivity period of 12 years. Amortization of intangible assets during each of thenext five years is estimated to be approximately $5.0 million per year. The Company performed its annual impairment test as of October 1, 2018. TheCompany performed a qualitative assessment to evaluate whether there was an impairment of the assets. This assessment did not identify any indicators ofimpairment of the intangible assets as of that date.A rollforward of the Company's intangible assets for the years ended December 31, 2018 and 2017 follows: 2018Intangible AssetJanuary 1,AdditionsAmortizationDecember 31,Acquired ARIKAYCE R&D$58,200$—$(1,212)$56,988PARI milestone upon FDA approval—1,724(37)1,687 $58,200$1,724$(1,249)$58,675 2017Intangible AssetJanuary 1,AdditionsAmortizationDecember 31,Acquired ARIKAYCE IPRD$58,200$—$—$58,200 $58,200$—$—$58,2006. Fixed Assets, netFixed assets are stated at cost and depreciated using the straight-line method, based on useful lives as follows: EstimatedUseful Life (years) As of December 31,Asset Description 2018 2017 (in thousands)Lab equipment7 $7,935 $7,055Furniture and fixtures7 2,320 1,937Computer hardware and software3 - 5 3,796 2,325Office equipment7 65 65Manufacturing equipment7 1,166 1,436Leasehold improvementslease term 7,202 6,939Construction in progress (CIP)—14,3253,320 36,809 23,077Less accumulated depreciation (14,173) (10,645)Fixed assets, net $22,636 $12,432Depreciation expense was $3.6 million, $2.9 million and $2.4 million for the years ended December 31, 2018, 2017 and 2016, respectively.Fixed assets, net of depreciation, increased to $22.6 million during the year ended December 31, 2018 from $12.4 million in 2017. The $10.2million increase was primarily due to $11.0 million in construction in progress related to the long-term capacity build-out at the Patheon manufacturingfacility.89Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)7. Debt (Continued)7. DebtIn January 2018, the Company completed an underwritten public offering of the Convertible Notes, in which the Company sold $450.0 millionaggregate principal amount of Convertible Notes, including the exercise in full of the underwriters' option to purchase additional Convertible Notes of $50.0million. The Company's net proceeds from the offering, after deducting underwriting discounts and commissions and other offering expenses of $14.2million, were approximately $435.8 million. The Convertible Notes bear interest payable semiannually in arrears on January 15 and July 15 of each year,beginning on July 15, 2018. The Convertible Notes mature on January 15, 2025, unless earlier converted, redeemed, or repurchased.On or after October 15, 2024, until the close of business on the second scheduled trading day immediately preceding January 15, 2025, holders mayconvert their Convertible Notes at any time. Upon conversion, holders may receive cash, shares of the Company's common stock or a combination of cashand shares of the Company's common stock, at the Company's option. The initial conversion rate is 25.5384 shares of common stock per $1,000 principalamount of Convertible Notes (equivalent to an initial conversion price of approximately $39.16 per share of common stock). The conversion rate will besubject to adjustment in some events but will not be adjusted for any accrued and unpaid interest.Holders may convert their Convertible Notes prior to October 15, 2024, only under the following circumstances, subject to the conditions set forthin an indenture, dated as of January 26, 2018, between the Company and Wells Fargo Bank, National Association (Wells Fargo), as trustee, as supplementedby the first supplemental indenture, dated January 26, 2018, between the Company and Wells Fargo (as supplemented, the Indenture): (i) during the fivebusiness day period immediately after any five consecutive trading day period (the measurement period) in which the trading price per $1,000 principalamount of convertible notes, as determined following a request by a holder of the convertible notes, for each trading day of the measurement period was lessthan 98% of the product of the last reported sale price of the common stock and the conversion rate on such trading day, (ii) the Company elects to distributeto all or substantially all holders of the common stock (a) any rights, options or warrants (other than in connection with a stockholder rights plan for so longas the rights issued under such plan have not detached from the associated shares of common stock) entitling them, for a period of not more than 45 days fromthe declaration date for such distribution, to subscribe for or purchase shares of common stock at a price per share that is less than the average of the lastreported sale prices of the common stock for the 10 consecutive trading day period ending on, and including, the trading day immediately preceding thedeclaration date for such distribution, or (b) the Company’s assets, debt securities or rights to purchase securities of the Company, which distribution has aper share value, as reasonably determined by the board of directors, exceeding 10% of the last reported sale price of the common stock on the trading dayimmediately preceding the declaration date for such distribution, (iii) if a transaction or event that constitutes a fundamental change or a make-wholefundamental change occurs, or if the Company is a party to (a) a consolidation, merger, combination, statutory or binding share exchange or similartransaction, pursuant to which the common stock would be converted into, or exchanged for, cash, securities or other property or assets, or (b) any sale,conveyance, lease or other transfer or similar transaction in one transaction or a series of transactions of all or substantially all of the consolidated assets ofthe Company and its subsidiaries, taken as a whole, all or any portion of the Convertible Notes may be surrendered by a holder for conversion at any timefrom or after the date that is 30 scheduled trading days prior to the anticipated effective date of the transaction, (iv) if during any calendar quartercommencing after the calendar quarter ending on March 31, 2018 (and only during such calendar quarter), the last reported sale price of the common stockfor at least 20 trading days (whether or not consecutive) during the period of 30 consecutive trading days ending on the last trading day of the immediatelypreceding calendar quarter is greater than or equal to 130% of the conversion price on each applicable trading day, or, (v) if the Company sends a notice ofredemption, a holder may surrender all or any portion of its Convertible Notes, to which the notice of redemption relates, for conversion at any time on orafter the date the applicable notice of redemption was sent until the close of business on (a) the second business day immediately preceding the relatedredemption date or (b) if the Company fails to pay the redemption price on the redemption date as specified in such notice of redemption, such later date onwhich the redemption price is paid. The Convertible Notes can be settled in cash, common stock, or a combination of cash and common stock at the Company's option, and thus, theCompany determined the embedded conversion options in the convertible notes are not required to be separately accounted for as a derivative. However,since the Convertible Notes are within the scope of the accounting guidance for cash convertible instruments, the Company is required to separate theConvertible Notes into liability and equity components. The carrying amount of the liability component was calculated by measuring the fair value of asimilar liability that does not have an associated equity component. The fair value was based on data from readily available pricing90Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)7. Debt (Continued)sources which utilize market observable inputs and other characteristics for similar types of instruments. The carrying amount of the equity componentrepresenting the embedded conversion option was determined by deducting the fair value of the liability component from the gross proceeds of theConvertible Notes. The excess of the principal amount of the liability component over its carrying amount is amortized to interest expense over the expectedlife of a similar liability that does not have an associated equity component using the effective interest method. The equity component is not remeasured aslong as it continues to meet the conditions for equity classification in the accounting guidance for contracts in an entity’s own equity. The fair value of theliability component of the Convertible Notes on the date of issuance was estimated at $309.1 million using an effective interest rate of 7.6%, andaccordingly, the residual equity component on the date of issuance was $140.9 million. The discount is being amortized to interest expense over the term ofthe Convertible Notes and has a remaining period of approximately 6.04 years.For the twelve months ended December 31, 2018, total interest expense related to the Convertible Notes was $25.5 million, which includes thecontractual interest coupon payable semi-annually in cash, the amortization of the issuance costs, and accretion of debt discount, as described in the tablebelow. The following table presents the carrying value of the Company’s debt balance as of December 31, 2018 (in thousands): As of December 31,2018 1.75% convertible senior notes due 2025$450,000 Debt issuance costs, unamortized(8,440) Discount on debt(125,002)Long-term debt, net$316,558As of December 31, 2018, future principal repayments of the debt for each of the fiscal years through maturity were as follows (in thousands): Year Ending December 31:2019$—2020—2021—2022—2023 and thereafter450,000$450,000 In February 2018, the Company used part of the net proceeds from the issuance of the Convertible Notes to pay off its outstanding debt to HerculesCapital (Hercules). The payments to Hercules consisted of $55.0 million for the principal amount and an additional $3.2 million in back-end fees,outstanding interest, and prepayment penalty fees, which resulted in a $2.2 million loss on extinguishment of debt in the quarter ended March 31, 2018. The estimated fair value of the debt (categorized as a Level 2 liability for fair value measurement purposes) is determined using current marketfactors and the ability of the Company to obtain debt at comparable terms to those that are currently in place. As of December 31, 2018 and 2017, the fairvalue of the Company's debt approximated the carrying amount.8. Shareholders' EquityCommon Stock—As of December 31, 2018, the Company had 500,000,000 shares of common stock authorized with a par value of $0.01 and77,307,521 shares of common stock issued and outstanding. In addition, as of December 31, 2018, the Company had reserved 9,381,730 shares of commonstock for issuance upon the exercise of outstanding common stock options and 227,826 shares of common stock for issuance upon the vesting of restrictedstock units.91Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)In September 2017, the Company completed an underwritten public offering of 14,123,150 shares of the Company’s common stock, which includedthe underwriter’s exercise in full of its over-allotment option of 1,842,150 shares, at a price to the public of $28.50 per share. The Company’s net proceedsfrom the sale of the shares, after deducting underwriting discounts and offering expenses of $24.8 million, were approximately $377.7 million.Preferred Stock—As of December 31, 2018 and 2017, the Company had 200,000,000 shares of preferred stock authorized with a par value of $0.01and no shares of preferred stock were issued and outstanding.9. Stock-Based CompensationThe Company’s current equity compensation plan, the 2017 Incentive Plan, was approved by shareholders at the Company’s Annual Meeting ofShareholders on May 18, 2017. The 2017 Incentive Plan is administered by the Compensation Committee and the Board of Directors of the Company. Underthe terms of the 2017 Incentive Plan, the Company is authorized to grant a variety of incentive awards based on its common stock, including stock options(both incentive stock options and non-qualified stock options), RSUs, performance options/shares and other stock awards, as well as pay incentive bonuses toeligible employees and non-employee directors. On May 18, 2017, upon the approval of the 2017 Incentive Plan by shareholders, 5,000,000 shares wereauthorized for issuance thereunder, plus any shares subject to then-outstanding awards under the 2015 Incentive Plan and the 2013 Incentive Plan thatsubsequently were canceled, terminated unearned, expired, were forfeited, lapsed for any reason or were settled in cash without the delivery of shares. Asof December 31, 2018, 3,622,830 shares remained for future issuance under the 2017 Incentive Plan. The 2017 Incentive Plan will terminate on April 3, 2027unless it is extended or terminated earlier pursuant to its terms. In addition, from time to time, the Company makes inducement grants of stock options. Theseawards are made pursuant to the Nasdaq inducement grant exception as a component of new hires’ employment compensation in connection with theCompany’s equity grant program. During the twelve months ended December 31, 2018 and 2017, the Company granted inducement stock options covering295,720 and 266,230, respectively, shares of the Company's common stock to new employees.Stock Options—The Company calculates the fair value of stock options granted using the Black-Scholes valuation model. The following tablesummarizes the grant date fair value and assumptions used in determining the fair value of all stock options granted, including grants of inducement options,during the years ended December 31, 2018, 2017 and 2016. 2018 2017 2016Volatility66% - 68% 71% - 79% 74% - 77%Risk-free interest rate2.25% - 2.96% 1.73% - 2.13% 1.00% - 1.90%Dividend yield0.0% 0.0% 0.0%Expected option term (in years)5.09 6.25 6.25Weighted average fair value of stock options granted$16.03 $10.52 $8.77For the years ended December 31, 2018, 2017 and 2016, the volatility factor was based on the Company’s historical volatility during the expectedoption term. Estimated forfeitures were based on the actual percentage of option forfeitures since the closing of the Company’s merger with Transave, Inc. inDecember 2010 for the year ended 2016. Beginning with the year ended December 31, 2017, estimated forfeitures were based on the actual percentage ofoption forfeitures over the expected option term.From time to time, the Company grants performance-condition options to certain employees. Vesting of these options is subject to the Companyachieving certain performance criteria established at the date of grant and the individuals fulfilling a service condition (continued employment). As a resultof the FDA approval of ARIKAYCE in September 2018, the vesting of performance options totaling $1.1 million was recorded as non-cash compensationexpense in the third quarter of 2018.92Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)9. Stock-Based Compensation (Continued)The following table summarizes stock option activity for stock options granted for the years ended December 31, 2018, 2017 and 2016 as follows: Number ofShares WeightedAverageExercisePrice WeightedAverageRemainingContractualLife in Years AggregateIntrinsicValue(in '000)Options outstanding at January 1, 20165,273,722 $13.64 Granted2,532,675 $12.96 Exercised(162,340) $6.68 Forfeited and expired(527,351) $17.08 Options outstanding at December 31, 20167,116,706 $13.30 Vested and expected to vest at December 31, 20166,850,658 $13.25 Exercisable at December 31, 20163,113,998 $11.28 Options outstanding at December 31, 20167,116,706 $13.30 Granted2,284,710 $15.92 Exercised(378,275) $9.08 Forfeited and expired(414,220) $15.50 Options outstanding at December 31, 20178,608,921 $14.08 Vested and expected to vest at December 31, 20178,325,255 $14.03 Exercisable at December 31, 20174,229,478 $12.71 Options outstanding at December 31, 20178,608,921 $14.08 Granted1,755,600 $27.63 Exercised(494,351) $14.46 Forfeited and expired(488,440) $19.79 Options outstanding at December 31, 20189,381,730 $16.30 6.69 $13,052Vested and expected to vest at December 31, 20188,693,635 $15.90 6.51 $12,926Exercisable at December 31, 20185,649,698 $13.45 5.58 $12,181The total intrinsic value of stock options exercised during the years ended December 31, 2018, 2017 and 2016 was $5.6 million, $4.3 million and$1.0 million, respectively.As of December 31, 2018, there was $29.7 million of unrecognized compensation expense related to unvested stock options, which is expected tobe recognized over a weighted average period of 2.4 years. The following table summarizes the range of exercise prices and the number of stock optionsoutstanding and exercisable as of December 31, 2018:93Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)9. Stock-Based Compensation (Continued)Outstanding as of December 31, 2018 Exercisable as ofDecember 31, 2018Range ofExercise Prices Number ofOptions WeightedAverageRemainingContractual Term(in years) WeightedAverageExercise Price Number ofOptions WeightedAverageExercisePrice$3.03 $4.55 960,038 3.62 $3.60 960,038 $3.60$6.90 $6.90 120,403 4.13 $6.90 120,403 $6.90$6.96 $10.85 953,089 6.85 $10.76 604,037 $10.71$11.14 $12.58 947,839 4.72 $12.17 887,207 $12.18$12.66 $13.94 967,420 7.31 $13.62 455,114 $13.59$14.24 $16.07 1,142,513 5.76 $15.31 782,818 $15.22$16.09 $17.16 1,380,220 7.58 $16.69 687,691 $16.57$17.24 $22.76 1,387,909 6.51 $21.04 1,081,677 $21.31$22.84 $30.46 1,355,366 8.37 $28.54 57,644 $25.41$30.86 $32.46 166,933 8.60 $31.20 13,069 $31.57Restricted Stock and Restricted Stock Units—The Company may grant Restricted Stock (RS) and Restricted Stock Units (RSUs) to employees andnon-employee directors. Each share of RS vests upon and each RSU represents a right to receive one share of the Company's common stock upon thecompletion of a specific period of continued service.RS and RSU awards granted are valued at the market price of the Company's common stock on the date of grant. The Company recognizes noncashcompensation expense for the fair values of these RS and RSUs on a straight-line basis over the requisite service period of these awards.The following table summarizes RSU awards granted during the years ended December 31, 2018, 2017 and 2016: Number ofRSUs WeightedAverageGrant PriceOutstanding at January 1, 2016 43,554 $19.47Granted 89,194 $10.85Released (43,554) $16.07Forfeited — $—Outstanding at December 31, 2016 89,194 $10.85Granted 46,914 $17.16Released (89,194) $10.85Forfeited — $—Outstanding at December 31, 2017 46,914 $17.16Granted 253,586 $29.16Released (51,992) $18.46Forfeited (20,682) $29.05Outstanding at December 31, 2018 227,826 $29.1494Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)9. Stock-Based Compensation (Continued)As of December 31, 2018, there was $3.4 million of unrecognized compensation expense related to unvested awards, which is expected to berecognized over a weighted average period of 2.8 years.The following table summarizes the stock-based compensation recorded in the consolidated statements of comprehensive loss related to stockoptions and RSUs during the years ended December 31, 2018, 2017 and 2016 (in millions): 2018 2017 2016Research and development expenses$9.4 $6.5 $6.2Selling, general and administrative expenses16.8 11.6 11.8Total (1)$26.2 $18.1 $18.0_________________________________(1)Includes $0.0 million, $0.0 million and $1.7 million for the years ended December 31, 2018, 2017 and 2016, respectively, for the remeasurement ofcertain stock options and RSUs that occurred during May 2013.Employee Stock Purchase Plan - On May 15, 2018, the Company's shareholders approved the Company’s 2018 Employee Stock Purchase Plan(ESPP). As part of the ESPP, eligible employees may acquire an ownership interest in the Company by purchasing common stock, at a discount, throughpayroll deductions. The ESPP is compensatory under GAAP and the Company recorded stock compensation expense of $0.9 million in 2018.10. Income TaxesThe income tax provision (benefit) was $0.2 million, $(0.3) million and $0.1 million and the effective rates were approximately 0%, 0% and 0% forthe years ended December 31, 2018, 2017 and 2016, respectively. The income tax (benefit) for the year ended December 31, 2017 reflects the reversal of thevaluation allowance related to alternative minimum tax (AMT) that the Company paid in 2009. As a result of the Tax Cuts and Jobs Act (the Tax Act), theCompany recorded a noncurrent receivable to reflect the refund due to the Company in future periods relating to the previously paid AMT. In addition, theincome tax provision (benefit) for the years ended December 31, 2018, 2017 and 2016 reflected current income tax expense recorded as a result of the taxableincome in certain of the Company's non-US subsidiaries.For the years ended December 31, 2018 and 2017, the Company was also subject to foreign income taxes as a result of legal entities established foractivities in Europe and Japan. The Company's loss before income taxes in the US and globally was as follows (in thousands): Years Ended December 31,2018 2017 2016US$(286,211) $(136,682) $(140,354)Foreign(37,865) (56,239) (35,821)Total$(324,076) $(192,921) $(176,175)95Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)10. Income Taxes (Continued)The Company's income tax (benefit) provision consisted of the following (in thousands): Years Ended December 31, 2018 2017 2016Current: Federal$— $— $—State4 3 3Foreign197 142 95 201 145 98Deferred: Federal— (417) —State— — —Foreign— — — — (417) —Total$201 $(272) $98The reconciliation between the federal statutory tax rates and the Company's effective tax rate is as follows: Years Ended December 31, 2018 2017 2016Statutory federal tax rate21 % 34 % 34 %Permanent items— % (3)% (3)%State income taxes, net of federal benefit5 % 4 % 4 %R&D and other tax credits2 % 8 % 8 %Foreign income taxes(1)% (6)% (4)%Impact of Tax Act— % (49)% — %Change in valuation allowance(27)% 12 % (39)%Other— % — % — %Effective tax rate— % — % — %96Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)10. Income Taxes (Continued)Deferred tax assets and liabilities are determined based on the difference between financial statement and tax bases using enacted tax rates in effectfor the year in which the differences are expected to reverse. The components of the deferred tax assets and liabilities consist of the following: As of December 31, 2018 2017Deferred tax assets: Net operating loss carryforwards$231,918 $186,342General business credits109,502 66,371Product license6,902 7,730Inventory7,651 —Other24,855 17,217Gross deferred tax assets$380,828 $277,660Deferred tax liabilities: Intangibles$(15,424) $(16,360)Convertible debt(32,799) —Deferred tax liabilities$(48,223) $(16,360)Net deferred tax assets$332,605 $261,300Valuation allowance(332,605) (261,300)Net deferred tax assets$— $—The net deferred tax assets (prior to applying the valuation allowance) of $332.6 million and $261.3 million at December 31, 2018 and 2017,respectively, primarily consist of net operating loss carryforwards for income tax purposes. Due to the Company's history of operating losses, the Companyrecorded a full valuation allowance on its net deferred tax assets by increasing the valuation allowance by $71.3 million in 2018 and decreasing by $23.3million in 2017, respectively, as it was more likely than not that such tax benefits will not be realized. As of December 31, 2017, the Company's grossdeferred tax assets were also impacted by the Tax Act which required the change to a 21% US tax rate (see below for further discussion on the Tax Act).At December 31, 2018, the Company had federal net operating loss carryforwards for income tax purposes of approximately $880.6 million. Due tothe limitation on NOLs as more fully discussed below, $709.7 million of the NOLs are available to offset future taxable income, if any. The NOL carryoversand general business tax credits expire in various years beginning in 2018. For state tax purposes, the Company has approximately $515.3 million of NewJersey NOLs available to offset against future taxable income. The Company also has California and Virginia NOLs that are entirely limited due toSection 382 (as discussed below).From 2014 through 2017, the Company completed an Internal Revenue Code Section 382 (Section 382) analysis in order to determine the amountof losses that are currently available for potential offset against future taxable income, if any. It was determined that the utilization of the Company's NOLand general business tax credit carryforwards generated in tax periods up to and including December 2010 were subject to substantial limitations underSection 382 due to ownership changes that occurred at various points from the Company's original organization through December 2010. In general, anownership change, as defined by Section 382, results from transactions increasing the ownership of shareholders that own, directly or indirectly, 5% or moreof a corporation's stock, in the stock of a corporation by more than 50 percentage points over a testing period (usually 3 years). Since the Company'sformation, it has raised capital through the issuance of common stock on several occasions which, combined with the purchasing shareholders' subsequentdisposition of those shares, have resulted in multiple changes in ownership, as defined by Section 382, since the Company's formation in 1999. Theseownership changes resulted in substantial limitations on the use of the Company's NOLs and general business tax credit carryforwards up to and includingDecember 2010. The Company continues to track all of its NOLs and tax credit carryforwards but has provided a full valuation allowance to offset thoseamounts.97Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)10. Income Taxes (Continued)On December 22, 2017, the US government enacted the Tax Act. The Tax Act significantly revises US tax law by, among other provisions, loweringthe US federal statutory income tax rate from 35% to 21%, imposing a mandatory one-time transition tax on previously deferred foreign earnings, andeliminating or reducing certain income tax deductions.The Tax ActASC 740, Income Taxes requires the effects of changes in tax laws to be recognized in the period in which the legislation is enacted. However, due tothe complexity and significance of the Tax Act’s provisions, the SEC staff issued SAB 118, which allowed companies to record the tax effects of the Tax Acton a provisional basis based on a reasonable estimate, and then, if necessary, subsequently adjust such amounts during a limited measurement period as moreinformation becomes available.The Tax Act did not have a material impact on the Company's financial statements because its deferred temporary differences are fully offset by avaluation allowance and the Company does not have any significant offshore earnings from which to record the mandatory transition tax. The Companycompleted its analysis during the fourth quarter of 2018 and no additional tax effects of the Act were required to be recorded for the year ended December 31,2018.The financial statement recognition of the benefit for a tax position is dependent upon the benefit being more likely than not to be sustainable uponaudit by the applicable taxing authority. If this threshold is met, the tax benefit is then measured and recognized at the largest amount that is greater than50% likely of being realized upon ultimate settlement. If such unrecognized tax benefits were realized and not subject to valuation allowances, we wouldrecognize a tax benefit of $4.1 million. The following table summarizes the gross amounts of unrecognized tax benefits (in thousands): Net Deferred Tax AssetsBalance as of January 1,$— $—Additions related to prior period tax positions3,345 —Additions related to current period tax positions742 —Balance as of December 31,$4,087 $—The Company is subject to US federal and state income taxes and the statute of limitations for tax audit is open for the federal tax returns for theyears ended 2014 and later, and is generally open for certain states for the years 2013 and later. The Company has incurred net operating losses sinceinception, except for the year ended December 31, 2009. Such loss carryforwards would be subject to audit in any tax year in which those losses are utilized,notwithstanding the year of origin.The Company's policy is to recognize interest accrued related to unrecognized tax benefits and penalties in income tax expense. The Company hasrecorded no such expense. As of December 31, 2018 and 2017, the Company has recorded reserves for unrecognized income tax benefits of $4.1 million and$0.0 million, respectively. As any adjustment to the Company’s uncertain tax positions would not result in a cash tax liability, it has not recorded anyaccrued interest or penalties related to its uncertain tax positions. The Company does not anticipate any material changes in the amount of unrecognized taxpositions over the next 12 months.98Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)11. License and Other AgreementsIn-License AgreementsPARI Pharma GmbH—In April 2008, the Company entered into a licensing agreement with PARI Pharma GmbH (PARI) for use of the optimizedLamira Nebulizer System for delivery of ARIKAYCE in treating patients with NTM lung infections, CF and bronchiectasis. Under the licensing agreement,the Company has rights under several US and foreign issued patents and patent applications involving improvements to the optimized Lamira NebulizerSystem, to exploit such system with ARIKAYCE for the treatment of such indications, but the Company cannot manufacture such nebulizers except aspermitted under the Commercialization Agreement with PARI. Under the licensing agreement, the Company paid PARI an upfront license fee and certainmilestone payments. Upon FDA acceptance of the Company's New Drug Application and the subsequent FDA approval of ARIKAYCE, the Company paidPARI additional milestone payments of €1.0 million and €1.5 million, respectively. In addition, PARI is entitled to receive a future milestone payment of€0.5 million in cash based on achievement of first receipt of marketing approval in a major EU country for ARIKAYCE and the device. PARI is entitled toreceive royalty payments in the mid-single digits on the annual global net sales of ARIKAYCE, pursuant to the licensing agreement, subject to certainspecified annual minimum royalties. In October 2017, the Company exercised an option to buy-down the royalties that will be paid to PARI on ARIKAYCEnet sales. The payment to PARI was included as a component of SG&A expenses in the fourth quarter of 2017. See below for information related to thecommercialization agreement with PARI.Other AgreementsCystic Fibrosis Foundation Therapeutics, Inc.—In 2004 and 2009, the Company entered into research funding agreements with Cystic FibrosisFoundation Therapeutics, Inc. (CFFT) whereby it received $1.7 million and $2.2 million for each respective agreement in research funding for thedevelopment of ARIKAYCE. If ARIKAYCE becomes an approved product for certain infections in CF patients or such infections in human pulmonarydisease in the US, the Company will owe a payment to CFFT of up to $13.4 million that is payable over a three-year period after regulatory approval in theUS. Furthermore, if certain global sales milestones are met within five years of the drug's commercialization, the Company would owe an additional paymentof $3.9 million. Because there is significant development and regulatory risk associated with ARIKAYCE, including with respect to the CF indication, theCompany has not accrued these obligations.Therapure Biopharma Inc.—In February 2014, the Company entered into a contract manufacturing agreement with Therapure Biopharma Inc.(Therapure) for the manufacture of ARIKAYCE, on a non-exclusive basis, at a 200 kg scale. Pursuant to the agreement, the Company and Therapurecollaborated to construct a production area for the manufacture of ARIKAYCE in Therapure's existing manufacturing facility in Canada. The agreement hasan initial term of five years, which began in October 2018, and will renew automatically for successive periods of two years each, unless terminated by eitherparty by providing the required two years prior written notice to the other party. Notwithstanding the foregoing, the parties have rights and obligations underthe agreement prior to the commencement of the initial term. Under the agreement, the Company is obligated to pay certain minimum amounts for thebatches of ARIKAYCE produced each calendar year.PARI Pharma GmbH—In July 2014, the Company entered into a Commercialization Agreement with PARI for the manufacture and supply ofLamira Nebulizer Systems and related accessories (the Device) as optimized for use with ARIKAYCE. Under the Commercialization Agreement, PARImanufactures the Device except in the case of certain defined supply failures, when the Company will have the right to make the Device and have it made bythird parties (but not certain third parties deemed under the Commercialization Agreement to compete with PARI). The Commercialization Agreement has aninitial term of fifteen years from the first commercial sale of ARIKAYCE in October 2018 (the Initial Term). The term of the agreement may be extended bythe Company for an additional five years by providing written notice to PARI at least one year prior to the expiration of the Initial Term. Notwithstanding theforegoing, the parties have certain rights and obligations under the agreement prior to the commencement of the Initial Term.SynteractHCR, Inc.—In December 2014, the Company entered into a services agreement with SynteractHCR, Inc. (Synteract) pursuant to which theCompany retained Synteract to perform implementation and management services in connection with the CONVERT study. The Company anticipates thataggregate costs relating to all work orders for the CONVERT study will be approximately $48 million over the period of the study. In April 2015, theCompany entered into a work order with Synteract to perform implementation and management services for the completed 312 study.Ajinomoto Althea, Inc.—In September 2015, the Company entered into a Commercial Fill/Finish Services Agreement (the Fill/Finish Agreement)with Ajinomoto Althea, Inc., a Delaware corporation (Althea), for Althea to produce, on a non-99Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)11. License and Other Agreements (Continued)exclusive basis, ARIKAYCE in finished dosage form at a 50 kg scale. Under the Fill/Finish Agreement, the Company is obligated to pay a minimum of $2.7million for the batches of ARIKAYCE produced by Althea each calendar year during the term of the Fill/Finish Agreement. The Fill/Finish Agreementbecame effective as of January 1, 2015, and following an extension in 2018, is expected to remain in effect through December 31, 2021. The Fill/FinishAgreement may be extended for additional two-year periods upon mutual written agreement of the Company and Althea at least one year prior to theexpiration of its then-current term. The Company has expensed at least the required minimum in each year of the contract.AstraZeneca AB—In October 2016, the Company entered into a license agreement (AZ License Agreement) with AstraZeneca AB, a Swedishcorporation (AstraZeneca). Pursuant to the terms of the AZ License Agreement, AstraZeneca granted the Company exclusive global rights for the purpose ofdeveloping and commercializing AZD7986 (renamed INS 1007). In consideration of the licenses and other rights granted by AstraZeneca, the Companymade an upfront payment of $30.0 million, which was included as research and development expense in the fourth quarter of 2016. The Company is alsoobligated to make a series of contingent milestone payments totaling up to an additional $85.0 million upon the achievement of clinical development andregulatory filing milestones. If the Company elects to develop INS1007 for a second indication, the Company will be obligated to make an additional seriesof contingent milestone payments to AstraZeneca totaling up to $42.5 million. The Company is not obligated to make any additional milestone payments foradditional indications. In addition, the Company will pay AstraZeneca tiered royalties ranging from a high single-digit to mid-teens on net sales of anyapproved product based on INS1007 and one additional payment of $35.0 million upon the first achievement of $1.0 billion in annual net sales. The AZLicense Agreement provides AstraZeneca with the option to negotiate a future agreement with the Company for commercialization of INS1007 in chronicobstructive pulmonary disease or asthma.Patheon UK Limited—In October 2017, the Company entered into certain agreements with Patheon UK Limited (Patheon) related to the increase ofits long-term production capacity for ARIKAYCE commercial inventory. The agreements provide for Patheon to manufacture and supply ARIKAYCE for itsanticipated commercial needs. Under these agreements, the Company is required to deliver to Patheon the required raw materials, including activepharmaceutical ingredients, and certain fixed assets needed to manufacture ARIKAYCE. Patheon's supply obligations will commence once certaintechnology transfer and construction services are completed. The Company's manufacturing and supply agreement with Patheon will remain in effect for afixed initial term, after which it will continue for successive renewal terms unless either party has given written notice of termination. The technology transferagreement will expire when the parties agree that the technology transfer services have been completed. The agreements may also be terminated under certainother circumstances, including by either party due to a material uncured breach of the other party or the other party’s insolvency. These early terminationclauses may reduce the amounts due to the relevant parties. The investment in our long-term production capacity build-out, including under the Patheonagreements and related agreements or purchase orders with third parties for raw materials and fixed assets, is estimated to be approximately $60 million.Syneos Health—We entered into a services agreement with Syneos Health (Syneos) pursuant to which we retained Syneos to performimplementation and management services in connection with the WILLOW study. We may terminate the services agreement or any work order for any reasonand without cause with 30 days' written notice. Either party may terminate the agreement in the event of a material breach or bankruptcy petition by the otherparty or, if any approval from a regulatory authority is revoked, suspended or expires without renewal. We anticipate that aggregate costs relating to all workorders for the WILLOW study will be approximately $21 million over the period of the study.12. Commitments and ContingenciesCommitmentsThe Company has an operating lease for office and laboratory space located in Bridgewater, NJ for which the initial lease term expires in November2019. Future minimum rental payments under this lease are $1.0 million. In July 2016, the Company signed an operating lease for additional laboratoryspace located in Bridgewater, NJ for which the initial lease term expires in September 2021. In October 2018, the Company expanded its lease for additionallaboratory space located in Bridgewater, NJ. Future minimum rental payments under this, and the initial lease, are $3.3 million. In September 2018, theCompany entered into a new lease for its new corporate headquarters in Bridgewater, NJ for which the initial lease term expires in June 2030. Futureminimum rental payments under this lease are $32.3 million.Rent expense charged to operations was $2.1 million, $1.5 million, and $1.2 million for the years ended December 31, 2018, 2017 and 2016,respectively. Rent expense is recorded on a straight-line basis over the term of the applicable leases.Future minimum lease payments under the Company's lease obligations as of December 31, 2018 are as follows (in thousands):Year Ending December 31: 2019$3,12520204,91920214,56820222,0272023 and thereafter24,036Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Total future minimum lease payments$38,675In addition to rent, the Company has several firm purchase commitments, primarily related to the manufacturing of ARIKAYCE and annualminimum royalties on global net sales of ARIKAYCE. Future firm purchase commitments under these agreements, the last of which ends in 2034, total $86.4million. These amounts do not represent our entire anticipated purchases in the future, but instead represent only purchases that are the subject ofcontractually obligated minimum purchases. The minimum commitments disclosed are determined based on noncancelable minimum spend amounts ortermination amounts. Additionally, we purchase products and services as needed with no firm commitment.Legal ProceedingsFrom time to time, the Company is a party to various lawsuits, claims and other legal proceedings that arise in the ordinary course of business. Whilethe outcomes of these matters are uncertain, management does not expect that the ultimate costs to resolve these matters will have a material adverse effect onthe Company’s consolidated financial position, results of operations or cash flows.13. Quarterly Financial Data (Unaudited)The following table summarizes unaudited quarterly financial data for the years ended December 31, 2018 and 2017 (in thousands, except pershare data). 2018 FirstQuarter SecondQuarter ThirdQuarter FourthQuarter TotalRevenues$— $— $— $9,835 $9,835Cost of product revenues*$— $— $— $2,423 $2,423Operating loss$(62,751) $(72,882) $(83,983) $(87,722) $(307,338)Net loss$(68,524) $(76,437) $(87,743) $(91,573) $(324,277)Basic and diluted net loss per share$(0.89) $(1.00) $(1.14) $(1.19) $(4.22) 100Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Table of ContentsINSMED INCORPORATEDNOTES TO CONSOLIDATED FINANCIAL STATEMENTS (Continued)13. Quarterly Financial Data (Unaudited) (Continued) 2017 FirstQuarter SecondQuarter ThirdQuarter FourthQuarter** Total**Revenues$— $— $— $— $—Cost of product revenues*$— $— $— $— $—Operating loss$(35,969) $(43,515) $(44,083) $(65,353) $(188,920)Net loss$(37,414) $(44,672) $(45,179) $(65,384) $(192,649)Basic and diluted net loss per share$(0.60) $(0.72) $(0.69) $(0.85) $(2.89)________________* Excludes amortization of intangible assets.** Includes a one-time payment in October 2017 related to the buy-down of royalties payable to PARI on the global net sales of ARIKAYCE.Basic and diluted net loss per share amounts included in the above table were computed independently for each of the quarters presented.Accordingly, the sum of the quarterly basic and diluted net loss per share amounts may not agree to the total for the year.14. Retirement PlanThe Company has a 401(k) defined contribution plan for the benefit for all US employees and permits voluntary contributions by employeessubject to IRS-imposed limitations. Effective January 1, 2018, the Company matched 100% of eligible employee contributions on the first 4% of employeesalary (up to the IRS maximum). Employer contributions for the year ended December 31, 2018, 2017 and 2016 were $2.2 million, $0.8 million and $0.6million, respectively. Prior to 2018, the Company matched 100% of eligible employee contributions on the first 3% of employee salary (up to the IRSmaximum).101Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. CONFIDENTIAL TREATMENT HAS BEEN REQUESTED AS TO CERTAIN PORTIONS OF THIS DOCUMENT.EACH SUCH PORTION, WHICH HAS BEEN OMITTED HEREIN AND REPLACED WITH ASTERISKS [***], HASBEEN FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION.Amendment No. 8To License Agreement BetweenINSMED INCORPORATED and PARI Pharma GmbHThis eighth amendment (“Amendment No. 8”) effective 19th December 2018 (“Amendment No. 8 Effective Date”) to theLicense Agreement dated and effective the 25th of April 2008 between PARI Pharma GmbH, a German corporation with a principalplace of business at Moosstrasse 3, D-82319 Starnberg, Germany (“PARI”) and Transave, Inc., a Delaware corporation, as amendedby Amendment No. 1 the 24th day of June 2009, Assignment and Amendment No. 2 the 22nd day of December 2010, AmendmentNo. 3 the 6th day of March 2012, Amendment No. 4 the 21st day of May 2012, Amendment No. 5 the 5th day of October 2015,Amendment No. 6 the 9th day of October 2015 and Amendment No. 7 the 21st day of July 2017 (collectively, the “Agreement”), isentered into between PARI and Insmed Incorporated (successor in interest to Transave, Inc.), with registered offices at 10 FinderneAvenue, Building 10, Bridgewater, NJ 08807-3365 (“Insmed”). PARI and Insmed shall be referred to collectively as the “Parties”.WHEREAS, the Parties entered into a certain commercialization agreement effective as of July 8th, 2014 (the“Commercialization Agreement”); andWHEREAS, the Parties now desire to amend the terms and conditions of the Agreement to reflect certain business discussionsbetween the Parties.NOW, THEREFORE, in consideration of the recitals set forth above, the mutual covenants, terms and conditions set forthbelow, and other good and valuable consideration, the receipt and sufficiency of which is hereby acknowledged, the Parties agree asfollows:1.Definitions. Capitalized terms used but not defined in this Amendment No. 8 shall have the meanings ascribed tothem in the Agreement.2.The Parties agree Section [***] of the Agreement is not applicable.3.A new Section 6.5 is hereby added which shall read as follows:“6.5 Training. [***]”4.Royalty Report. Section 9.2 of the Agreement is hereby amended by adding the following to the end of the section:“The report and calculation of royalties as set forth in this Section 9.2 of the Agreement shall contain a detailed listing of alldeductions (i) as set forth in the definition of the term “Net Sales”, (ii) [***] and (iii) [***]. A sample report and calculation ofroyalties, for example and illustrative purposes only, is attached as Exhibit 9.2.”5.Exhibit 9.2. The Agreement is hereby amended by adding the attached Exhibit 9.2 as Exhibit 9.2 to the Agreement.*** Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has beenrequested with respect to the omitted portions.Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. 6.Miscellaneous. Upon execution, this Amendment No. 8 shall be made part of the Agreement and shall beincorporated therein by reference. Except as provided herein, all other terms and conditions of the Agreement shall remain infull force and effect.- signature page follows -*** Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has beenrequested with respect to the omitted portions.Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. IN WITNESS WHEREOF, the Parties have executed this Amendment No. 8 as of the Amendment No. 8 Effective Dateindicated above.Insmed Incorporated PARI Pharma GmbHBy: /s/ William H. Lewis By: /s/ Dr. Martin Knoch Name: William H. Lewis Name: Dr. Martin Knoch Title: CEO & President Title: PresidentDate: December 21, 2018 Date: December 19, 2018 *** Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has beenrequested with respect to the omitted portions.Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Exhibit 9.2See attached page*** Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has beenrequested with respect to the omitted portions.Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. Note: Example purposes only for Royaltycalculations US Country A The report should be on a country-by-country basis (in accordance with Section9.2 of the License Agreement) All amounts in USD Arikyace Kits Arikyace Kits Notes Sold Sold Totals WAC (includes drug kit/aerosol head)[***] [***] [***] Units sold forQuarter [***] [***] [***] Gross sales invoiced[***] [***] [***] [***] Gross-to-net deductions[***] [***] [***] [***] Net sales-GAAP[***] [***] [***] [***] [***] [***][***][***] [***][***] [***] [***] [***][***][***] [***][***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] [***] Royalty owed to PARI for quarter [***] [***] Cash payment to PARI for applicable quarter [***] *** Certain information on this page has been omitted and filed separately with the Securities and Exchange Commission. Confidential treatment has beenrequested with respect to the omitted portions.Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. 10 Finderne Avenue, Building 10 | Bridgewater, NJ 08807 | Phone: 908-977-9900 | Fax: 908-526-4026 www.insmed.comDecember 18, 2018VIA E-MAILCraig LoganVP of Finance and Chief Financial OfficerAjinomoto Althea, Inc.11040 Roselle StreetSan Diego, CA 92121RE: Extension of Commercial Fill/Finish Services AgreementDear Mr. Logan,As you know, Ajinomoto Althea, Inc. (“Althea”) and Insmed Incorporated (“Insmed”) are parties to the Commercial Fill/Finish SupplyAgreement, dated January 1, 2015 (the “Agreement”). Per Section 7.1 of the Agreement, the Initial Term (as defined in the Agreement)of the Agreement was extended to, and now expires on, December 31, 2019 and the parties may mutually agree to extend theAgreement for an additional two (2) year period at least one (1) year prior to the expiration. Insmed kindly requests that Altheaacknowledge and agree to a two (2) year extension of the Agreement until December 31, 2021 by signing below.We appreciate all of the efforts made to date by Althea and look forward to continuing our relationship. Please contact me at 908-947-4309 with any questions.Sincerely,/s/ Don NocioloDon NocioloVice President, Technical OperationsAGREED AND ACKNOWLEDGED:Ajinomoto Althea, Inc.By: /s/ Craig W. Logan Name: Craig W. LoganTitle: VP of Finance and Chief Financial OfficerSource: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. EXHIBIT 21.1 LIST OF SUBSIDIARIES NameJurisdiction ofIncorporationCeltrix Pharmaceuticals, Inc.DelawareInsmed LimitedEngland and WalesInsmed Holdings LimitedIrelandInsmed Ireland LimitedIrelandInsmed Germany GmbHGermanyInsmed France SASFranceInsmed Netherlands B.V.NetherlandsInsmed Godo KaishaJapanInsmed Bermuda LimitedBermudaSource: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. EXHIBIT 23.1 Consent of Independent Registered Public Accounting Firm We consent to the incorporation by reference in the following Registration Statements:(1)Registration Statement on Form S-3 No. 333-218118 of Insmed Incorporated, and(2)Registration Statements on Form S-8 Nos. 333-39200, 333-87878, 333-129479, 333-175532, 333-188852, 333-204503, 33-218668 and 333-225323of Insmed Incorporated;of our reports dated February 22, 2019, with respect to the consolidated financial statements of Insmed Incorporated and the effectiveness of internal controlover financial reporting of Insmed Incorporated included in this Annual Report (Form 10-K) of Insmed Incorporated for the year ended December 31, 2018. /s/ Ernst & Young LLPIselin, New JerseyFebruary 22, 2019Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. EXHIBIT 31.1 Section 302 Certification I, William H. Lewis, Chairman and Chief Executive Officer of Insmed Incorporated, certify that:(1) I have reviewed this annual report on Form 10-K of Insmed Incorporated;(2) Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make thestatements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report;(3) Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects thefinancial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;(4) The registrant's other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in ExchangeAct Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrantand have:(a) Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, toensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within thoseentities, particularly during the period in which this report is being prepared;(b) Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under oursupervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for externalpurposes in accordance with generally accepted accounting principles;(c) Evaluated the effectiveness of the registrant's disclosure controls and procedures and presented in this report our conclusions about theeffectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and(d) Disclosed in this report any change in the registrant's internal control over financial reporting that occurred during the registrant's most recentfiscal quarter (the registrant's fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materiallyaffect, the registrant's internal control over financial reporting; and(5) The registrant's other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to theregistrant's auditors and the audit committee of the registrant's board of directors (or persons performing the equivalent functions):(a) All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonablylikely to adversely affect the registrant's ability to record, process, summarize and report financial information; and(b) Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant's internal controlover financial reporting.Date: February 22, 2019/s/ William H. LewisWilliam H. LewisChairman and Chief Executive Officer(Principal Executive Officer)Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. EXHIBIT 31.2 Section 302 Certification I, Paolo Tombesi, Chief Financial Officer of Insmed Incorporated, certify that:(1) I have reviewed this annual report on Form 10-K of Insmed Incorporated;(2) Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light of thecircumstances under which such statements were made, not misleading with respect to the period covered by this report;(3) Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results ofoperations and cash flows of the registrant as of, and for, the periods presented in this report;(4) The registrant's other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e)and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the registrant and have:(a) Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to ensure that materialinformation relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those entities, particularly during the period in whichthis report is being prepared;(b) Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our supervision, to providereasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally acceptedaccounting principles;(c) Evaluated the effectiveness of the registrant's disclosure controls and procedures and presented in this report our conclusions about the effectiveness of the disclosurecontrols and procedures, as of the end of the period covered by this report based on such evaluation; and(d) Disclosed in this report any change in the registrant's internal control over financial reporting that occurred during the registrant's most recent fiscal quarter (theregistrant's fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to materially affect, the registrant's internal control overfinancial reporting; and(5) The registrant's other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the registrant's auditors and theaudit committee of the registrant's board of directors (or persons performing the equivalent functions):(a) All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are reasonably likely to adverselyaffect the registrant's ability to record, process, summarize and report financial information; and(b) Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant's internal control over financialreporting.Date: February 22, 2019/s/ Paolo TombesiPaolo TombesiChief Financial Officer(Principal Financial and Accounting Officer)Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. EXHIBIT 32.1 CERTIFICATION PURSUANT TO 18 USC. SECTION 1350, AS ADOPTED PURSUANT TO SECTION 906 OF THE SARBANES-OXLEY ACT OF 2003 In connection with this Annual Report on Form 10-K of Insmed Incorporated (the "Company") for the period ended December 31, 2018 as filed with the Securities and ExchangeCommission on the date hereof (the "Report"), I, William H. Lewis, Chairman and Chief Executive Officer of the Company, certify, pursuant to 18 USC. § 1350, as adoptedpursuant to § 906 of the Sarbanes-Oxley Act of 2003, that:(1) the Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended; and(2) the information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company./s/ William H. LewisWilliam H. LewisChairman and Chief Executive Officer(Principal Executive Officer)February 22, 2019This certification accompanies the Form 10-K to which it relates, is not deemed filed with the Securities and Exchange Commission and is not to be incorporated by reference intoany filing of Insmed Incorporated under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended (whether made before or after the date of theForm 10-K), irrespective of any general incorporation language contained in such filing.Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results. EXHIBIT 32.2 CERTIFICATION PURSUANT TO 18 USC. SECTION 1350, AS ADOPTED PURSUANT TO SECTION 906 OF THE SARBANES-OXLEY ACT OF 2003 In connection with this Annual Report on Form 10-K of Insmed Incorporated (the "Company") for the period ended December 31, 2018 as filed with the Securities and ExchangeCommission on the date hereof (the "Report"), I, Paolo Tombesi, Chief Financial Officer of the Company, certify, pursuant to 18 USC. § 1350, as adopted pursuant to § 906 of theSarbanes-Oxley Act of 2003, that:(1) the Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended; and(2) the information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company./s/ Paolo TombesiPaolo TombesiChief Financial Officer(Principal Financial and Accounting Officer)February 22, 2019This certification accompanies the Form 10-K to which it relates, is not deemed filed with the Securities and Exchange Commission and is not to be incorporated by reference intoany filing of Insmed Incorporated under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended (whether made before or after the date of theForm 10-K), irrespective of any general incorporation language contained in such filing.Source: INSMED INC, 10-K, February 22, 2019Powered by Morningstar® Document Research℠The information contained herein may not be copied, adapted or distributed and is not warranted to be accurate, complete or timely. The user assumes all risks for any damages or losses arising from any use of this information,except to the extent such damages or losses cannot be limited or excluded by applicable law. Past financial performance is no guarantee of future results.

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