# EDGAR Filing Document

**Accession Number:** 0001104506
**File Stem:** 0001140361-23-000743
**Filing Date:** 2023-1
**Character Count:** 59999
**Document Hash:** c41e42f1cc3d04af7ed5f2e49787c221
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0001140361-23-000743.hdr.sgml**: 20230106

**ACCESSION NUMBER**: 0001140361-23-000743

**CONFORMED SUBMISSION TYPE**: 8-K

**PUBLIC DOCUMENT COUNT**: 35

**CONFORMED PERIOD OF REPORT**: 20230106

**ITEM INFORMATION**: Regulation FD Disclosure

**ITEM INFORMATION**: Financial Statements and Exhibits

**FILED AS OF DATE**: 20230106

**DATE AS OF CHANGE**: 20230106

**FILER**: 

**COMPANY DATA:**
- **COMPANY CONFORMED NAME:** INSMED Inc
- **CENTRAL INDEX KEY:** 0001104506
- **STANDARD INDUSTRIAL CLASSIFICATION:** PHARMACEUTICAL PREPARATIONS [2834]
- **IRS NUMBER:** 541972729
- **STATE OF INCORPORATION:** VA
- **FISCAL YEAR END:** 1231

**FILING VALUES:**
- **FORM TYPE:** 8-K
- **SEC ACT:** 1934 Act
- **SEC FILE NUMBER:** 000-30739
- **FILM NUMBER:** 23513766

**BUSINESS ADDRESS:**
- **STREET 1:** 700 US HIGHWAY 202/206
- **CITY:** BRIDGEWATER
- **STATE:** NJ
- **ZIP:** 08807
- **BUSINESS PHONE:** 908-977-9900

**MAIL ADDRESS:**
- **STREET 1:** 700 US HIGHWAY 202/206
- **CITY:** BRIDGEWATER
- **STATE:** NJ
- **ZIP:** 08807

**FORMER COMPANY:**
- **FORMER CONFORMED NAME:** INSMED INC
- **DATE OF NAME CHANGE:** 20000128

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### UNITED STATES

### SECURITIES AND EXCHANGE COMMISSION

#### Washington, D.C. 20549

### FORM 8-K

#### CURRENT REPORT

#### Pursuant to Section 13 or 15(d) of

#### The Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): January 6, 2023

## INSMED INCORPORATED
*(Exact name of registrant as specified in its charter)*

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| | | |
|:---|:---|:---|
| **Virginia**<br>| **000-30739**<br>| **54-1972729**<br>|
| *(State or other jurisdiction of incorporation)* | *(Commission File Number)* | *(IRS Employer Identification No.)* |

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| | |
|:---|:---|
| **700 US Highway 202/206**<br>**Bridgewater, New Jersey** | **08807**<br>*(Zip Code)* |
| *(Address of principal executive offices)* |  |

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Registrant's telephone number, including area code: **(908) 977-9900**

#### Not Applicable
*(Former name or former address, if changed since last report.)*

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

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| | | |
|:---|:---|:---|
| **Title of each class** | **Trading Symbol(s)** | **Name of each exchange on which registered** |
| Common Stock, par value $0.01 per share<br>| INSM<br>| Nasdaq Global Select Market<br>|

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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (17 CFR 230.405) or Rule 12b-2 of the Securities Exchange Act of 1934 (17 CFR 240.12b-2).

Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

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| | |
|:---|:---|
| **Item 7.01.** | **Regulation FD Disclosure.** |

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As previously announced, management of Insmed Incorporated (the "Company") will present at the virtual 41<sup>st</sup> Annual J.P. Morgan Healthcare Conference on Monday, January 9, 2023 at 4:30 p.m. PT (7:30 p.m. ET). A live webcast of the presentation will be accessible through the investor relations section of the Company's website. The slide presentation to be used during the presentation is attached hereto as Exhibit 99.1 and incorporated herein by reference.

On January 6, 2023, in connection with the presentation, the Company has issued a press release, a copy of which is attached hereto as Exhibit 99.1 and incorporated herein by reference. In addition, the slide presentation to be used during the presentation is attached hereto as Exhibit 99.2 and incorporated herein by reference.

The information contained in this Item 7.01, including the exhibits attached hereto, shall not be deemed "filed" for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the "Exchange Act"), or incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in such a filing.

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| | |
|:---|:---|
| **Item 9.01** | **Financial Statements and Exhibits.** |

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&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;(d) Exhibits.

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| | |
|:---|:---|
| **Exhibit**<br> **No.** | **Description** |
| [99.1](brhc10046302_99-1.htm) | Press release issued by Insmed Incorporated on January 6, 2023. |
| [99.2](brhc10046302_99-2.htm) | Insmed Incorporated J.P. Morgan Healthcare Conference Presentation. |
| 104 | Cover Page Interactive Date File (embedded within the Inline XBRL document). |

---

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#### SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

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| | | |
|:---|:---|:---|
|  | **INSMED INCORPORATED** | **INSMED INCORPORATED** |
| Dated: January 6, 2023 | By: | /s/ Michael Smith |
|  | Name: | Michael Smith |
|  | Title: | General Counsel and Corporate Secretary |

---

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## Exhibit 99.1

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 **Exhibit 99.1**<br>

![](image00001.jpg)

#### Insmed Provides Business Updates and Near-Term Strategic Outlook at 41<sup>st</sup> Annual J.P. Morgan Healthcare Conference

*—Topline Data from Phase 2 PK/PD Study of Brensocatib in Patients with Cystic Fibrosis Show Clear Dose Response at all Evaluated Doses—*

*—Treatment Discontinuation Rate of 15% Reported in Postmarketing ARISE Trial of ARIKAYCE<sup>®</sup> (amikacin liposome inhalation suspension) in Frontline Patients with MAC Lung Disease—Less than Half that of Pivotal Trial in Refractory Patients—*

*—Blended, Blinded Event Rate Ranging from 1.12 to 1.15 Events Per Patient Per Year Reported in Phase 3 ASPEN Trial of Brensocatib in Patients with Bronchiectasis, in Line with Expectations—*

*—Company Expects to Report 30% Global Revenue Growth for ARIKAYCE in 2022 Compared with 2021—*

*—2023 Global ARIKAYCE Revenues Expected to be Between $285 Million and $300 Million—*

BRIDGEWATER, N.J., January 6, 2023 /PRNewswire/ — Insmed Incorporated (Nasdaq:INSM), a global biopharmaceutical company on a mission to transform the lives of patients with serious and rare diseases, today provided an update on the Company's four pillars and outlined its near-term strategic priorities. These updates will be discussed as part of the Company's presentation at the 41<sup>st</sup> Annual J.P. Morgan Healthcare Conference in San Francisco on Monday, January 9, 2023, at 4:30 p.m. PT (7:30 p.m. ET).

"With a strong commercial engine, meaningful cash on hand, and a maturing pipeline with multiple near-term catalysts, Insmed is well-positioned to become one of the next great multiproduct biotechnology companies," said Will Lewis, Chair and Chief Executive Officer of Insmed. "The next 18 months will be the most critical period in our history as we share clinical data from across our pipeline and set the stage for sustainable growth that will enable us to go from serving tens of thousands of patients with serious and rare diseases to potentially more than 1 million. Importantly, we are very encouraged by the data we reported today from our Phase 2 PK/PD study of brensocatib in patients with cystic fibrosis, which show clear dose-dependent inhibition of neutrophil serine proteases across all doses and support the mechanism of action of this highly innovative potential therapy."

#### Strategic Priorities:

Insmed is focused on the following near-term strategic priorities:

• Control expenses by leveraging our reliable revenue stream while carefully deploying capital from significant cash on hand to advance our four pillars, concentrating more than 80% of expenditures on our mid- to late-stage pipeline and commercial business

<br> • Execute our mid- to late-stage clinical trials and produce topline clinical data readouts in the near term

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<br> • Advance commercial readiness activities as we prepare to potentially serve significantly more patients with serious and rare diseases

<br> • Initiate new clinical trials from our early-stage pipeline, including gene therapies

<br> • Continue to provide ARIKAYCE to appropriate patients with refractory nontuberculous mycobacterial lung disease caused by *Mycobacterium avium* complex (MAC)

#### Progress and Anticipated Milestones by Pillar:

*Pillar 1: ARIKAYCE*

• Insmed continues to expect full-year 2022 global revenues for ARIKAYCE to increase 30% year over year from 2021. For the full year 2023, Insmed anticipates ARIKAYCE global revenues will be between $285 million and $300 million.

• Insmed is advancing the development of ARIKAYCE in a frontline setting of patients newly diagnosed with MAC lung disease, consisting of the postmarketing confirmatory ARISE and ENCORE trials. Enrollment is complete in ARISE and Insmed anticipates sharing topline efficacy and safety data from the study in the third quarter of 2023. The Company today reported a treatment discontinuation rate in ARISE of 15%, which is less than half the discontinuation rate observed in the pivotal CONVERT trial of ARIKAYCE in patients with refractory MAC lung disease.

<br> • The Company continues to anticipate completing enrollment in ENCORE by the end of 2023.

*Pillar 2: Brensocatib*

• Enrollment remains on track in the Phase 3 ASPEN study, a global, randomized, double-blind, placebo-controlled trial to assess the efficacy, safety, and tolerability of brensocatib in patients with bronchiectasis. Insmed continues to anticipate completing enrollment in this trial in the first quarter of 2023 and sharing topline data in the second quarter of 2024. The Company today reported that the blended, blinded rate of pulmonary exacerbations in the ASPEN trial is in line with expectations, ranging from 1.12 to 1.15 events per patient per year in the most recent three months of the study.

• Insmed today reported topline data from the Phase 2 pharmacokinetic/pharmacodynamic study of brensocatib in patients with cystic fibrosis (CF). Researchers observed a clear dose-dependent and exposure-dependent inhibition of blood neutrophil serine proteases (NSPs) in patients treated with brensocatib across all doses in this study, consistent with the mechanism of action of brensocatib. Safety and tolerability were consistent with what was observed during the Phase 2 WILLOW study, with no significant drug-related findings. The Company concluded that an additional cohort evaluating a 65 mg dose of brensocatib is not needed in this patient population.

• As previously shared, Insmed plans to develop brensocatib in chronic rhinosinusitis without nasal polyps (CRSsNP), targeting severely affected patients. CRSsNP currently has no approved therapies and many patients do not respond to corticosteroids or endoscopic sinus surgery. Insmed anticipates moving brensocatib into Phase 2 development for CRSsNP by the middle of 2023.

*Pillar 3: TPIP*

<br> • Insmed is currently enrolling two Phase 2 studies of treprostinil palmitil inhalation powder (TPIP), one in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD) and the other in patients with pulmonary arterial hypertension (PAH).

<br> • The Company anticipates sharing interim, blinded dose titration and safety and tolerability data from the PH-ILD study in the second half of 2023. Topline results from the PH-ILD study continue to be expected to be shared in the first half of 2024.

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*Pillar 4: Early-Stage Research*

<br> • Insmed is advancing an early-stage research portfolio encompassing a wide range of technologies and modalities, including gene therapy, artificial intelligence-driven protein engineering, and protein manufacturing.

• The Company today announced that the initial therapeutic areas of focus for this pillar include musculoskeletal, central nervous system (CNS), ocular, and rheumatologic diseases. The first investigational new drug (IND) filing is expected to be completed in the first half of 2023. Preclinical data in musculoskeletal and CNS indications are also expected in the first half of 2023 and clinical data from the first trial in a musculoskeletal disease are anticipated in the first half of 2024.

<br> • Insmed anticipates having at least six IND applications filed or Phase 1 studies underway from this portfolio by the end of 2025.

<br> • The Company plans to provide an update on its early-stage research, including a deeper look at preclinical data across several target diseases, during a research day in the second quarter of 2023.

#### Presentation at the 41<sup>st</sup> Annual J.P. Morgan Healthcare Conference

Will Lewis, Chair and Chief Executive Officer of Insmed, will present at the 41<sup>st</sup> Annual J.P. Morgan Healthcare Conference on Monday, January 9, 2023, at 4:30 p.m. PT (7:30 p.m. ET). A live audio webcast of the presentation will be available on the Investor Relations section of the Company's website at www.insmed.com. A replay will also be archived for 90 days on the Investor Relations section of the site.

#### About ARIKAYCE

ARIKAYCE is approved in the United States as ARIKAYCE<sup>®</sup> (amikacin liposome inhalation suspension), in Europe as ARIKAYCE<sup>®</sup> Liposomal 590 mg Nebuliser Dispersion, and in Japan as ARIKAYCE<sup>®</sup> inhalation 590 mg (amikacin sulfate inhalation drug product). Current international treatment guidelines recommend the use of ARIKAYCE for appropriate patients. ARIKAYCE is a novel, inhaled, once-daily formulation of amikacin, an established antibiotic that was historically administered intravenously and associated with severe toxicity to hearing, balance, and kidney function. Insmed's proprietary PULMOVANCE<sup>®</sup> liposomal technology enables the delivery of amikacin directly to the lungs, where liposomal amikacin is taken up by lung macrophages where the infection resides, while limiting systemic exposure. ARIKAYCE is administered once daily using the Lamira<sup>®</sup> Nebulizer System manufactured by PARI Pharma GmbH (PARI).

#### About PARI Pharma and the Lamira<sup>®</sup> Nebulizer System

ARIKAYCE is delivered by a novel inhalation device, the Lamira<sup>®</sup> Nebulizer System, developed by PARI. Lamira<sup>®</sup> is a quiet, portable nebulizer that enables efficient aerosolization of ARIKAYCE via a vibrating, perforated membrane. Based on PARI's 100-year history working with aerosols, PARI is dedicated to advancing inhalation therapies by developing innovative delivery platforms to improve patient care.

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#### About Brensocatib

Brensocatib is a small molecule, oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP1) being developed by Insmed for the treatment of patients with bronchiectasis and other neutrophil-mediated diseases. DPP1 is an enzyme responsible for activating neutrophil serine proteases (NSPs), such as neutrophil elastase, in neutrophils when they are formed in the bone marrow. Neutrophils are the most common type of white blood cell and play an essential role in pathogen destruction and inflammatory mediation. In chronic inflammatory lung diseases, neutrophils accumulate in the airways and result in excessive active NSPs that cause lung destruction and inflammation. Brensocatib may decrease the damaging effects of inflammatory diseases such as bronchiectasis by inhibiting DPP1 and its activation of NSPs. Brensocatib is an investigational drug product that has not been approved for any indication in any jurisdiction.

#### About TPIP

Treprostinil palmitil inhalation powder (TPIP) is a dry powder formulation of treprostinil palmitil, a treprostinil prodrug consisting of treprostinil linked by an ester bond to a 16-carbon chain. Developed entirely in Insmed's laboratories, TPIP is a potentially highly differentiated prostanoid being evaluated for the treatment of patients with PAH, PH-ILD, and other rare and serious pulmonary disorders. TPIP is administered in a capsule-based inhalation device. TPIP is an investigational drug product that has not been approved for any indication in any jurisdiction.

#### IMPORTANT SAFETY INFORMATION FOR ARIKAYCE IN THE U.S.

#### WARNING: RISK OF INCREASED RESPIRATORY ADVERSE REACTIONS
**ARIKAYCE has been associated with an increased risk of respiratory adverse reactions, including hypersensitivity pneumonitis, hemoptysis, bronchospasm, and exacerbation of underlying pulmonary disease that have led to hospitalizations in some cases.**

**Hypersensitivity Pneumonitis** has been reported with the use of ARIKAYCE in the clinical trials. Hypersensitivity pneumonitis (reported as allergic alveolitis, pneumonitis, interstitial lung disease, allergic reaction to ARIKAYCE) was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (3.1%) compared to patients treated with a background regimen alone (0%). Most patients with hypersensitivity pneumonitis discontinued treatment with ARIKAYCE and received treatment with corticosteroids. If hypersensitivity pneumonitis occurs, discontinue ARIKAYCE and manage patients as medically appropriate*.*

**Hemoptysis** has been reported with the use of ARIKAYCE in the clinical trials. Hemoptysis was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (17.9%) compared to patients treated with a background regimen alone (12.5%). If hemoptysis occurs, manage patients as medically appropriate*.*

**Bronchospasm** has been reported with the use of ARIKAYCE in the clinical trials. Bronchospasm (reported as asthma, bronchial hyperreactivity, bronchospasm, dyspnea, dyspnea exertional, prolonged expiration, throat tightness, wheezing) was reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (28.7%) compared to patients treated with a background regimen alone (10.7%). If bronchospasm occurs during the use of ARIKAYCE, treat patients as medically appropriate*.*

**Exacerbations of underlying pulmonary disease** has been reported with the use of ARIKAYCE in the clinical trials. Exacerbations of underlying pulmonary disease (reported as chronic obstructive pulmonary disease (COPD), infective exacerbation of COPD, infective exacerbation of bronchiectasis) have been reported at a higher frequency in patients treated with ARIKAYCE plus background regimen (14.8%) compared to patients treated with background regimen alone (9.8%)*.* If exacerbations of underlying pulmonary disease occur during the use of ARIKAYCE, treat patients as medically appropriate*.*

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**Anaphylaxis and Hypersensitivity Reactions:** Serious and potentially life-threatening hypersensitivity reactions, including anaphylaxis, have been reported in patients taking ARIKAYCE. Signs and symptoms include acute onset of skin and mucosal tissue hypersensitivity reactions (hives, itching, flushing, swollen lips/tongue/uvula), respiratory difficulty (shortness of breath, wheezing, stridor, cough), gastrointestinal symptoms (nausea, vomiting, diarrhea, crampy abdominal pain), and cardiovascular signs and symptoms of anaphylaxis (tachycardia, low blood pressure, syncope, incontinence, dizziness). Before therapy with ARIKAYCE is instituted, evaluate for previous hypersensitivity reactions to aminoglycosides. If anaphylaxis or a hypersensitivity reaction occurs, discontinue ARIKAYCE and institute appropriate supportive measures.

**Ototoxicity** has been reported with the use of ARIKAYCE in the clinical trials. Ototoxicity (including deafness, dizziness, presyncope, tinnitus, and vertigo) were reported with a higher frequency in patients treated with ARIKAYCE plus background regimen (17%) compared to patients treated with background regimen alone (9.8%). This was primarily driven by tinnitus (7.6% in ARIKAYCE plus background regimen vs 0.9% in the background regimen alone arm) and dizziness (6.3% in ARIKAYCE plus background regimen vs 2.7% in the background regimen alone arm). Closely monitor patients with known or suspected auditory or vestibular dysfunction during treatment with ARIKAYCE. If ototoxicity occurs, manage patients as medically appropriate, including potentially discontinuing ARIKAYCE.

**Nephrotoxicity** was observed during the clinical trials of ARIKAYCE in patients with MAC lung disease but not at a higher frequency than background regimen alone. Nephrotoxicity has been associated with the aminoglycosides. Close monitoring of patients with known or suspected renal dysfunction may be needed when prescribing ARIKAYCE.

**Neuromuscular Blockade**: Patients with neuromuscular disorders were not enrolled in ARIKAYCE clinical trials. Patients with known or suspected neuromuscular disorders, such as myasthenia gravis, should be closely monitored since aminoglycosides may aggravate muscle weakness by blocking the release of acetylcholine at neuromuscular junctions.

**Embryo-Fetal Toxicity**: Aminoglycosides can cause fetal harm when administered to a pregnant woman. Aminoglycosides, including ARIKAYCE, may be associated with total, irreversible, bilateral congenital deafness in pediatric patients exposed *in utero*. Patients who use ARIKAYCE during pregnancy, or become pregnant while taking ARIKAYCE should be apprised of the potential hazard to the fetus.

**Contraindications**: ARIKAYCE is contraindicated in patients with known hypersensitivity to any aminoglycoside.

**Most Common Adverse Reactions**: The most common adverse reactions in Trial 1 at an incidence ≥5% for patients using ARIKAYCE plus background regimen compared to patients treated with background regimen alone were dysphonia (47% vs 1%), cough (39% vs 17%), bronchospasm (29% vs 11%), hemoptysis (18% vs 13%), ototoxicity (17% vs 10%), upper airway irritation (17% vs 2%), musculoskeletal pain (17% vs 8%), fatigue and asthenia (16% vs 10%), exacerbation of underlying pulmonary disease (15% vs 10%), diarrhea (13% vs 5%), nausea (12% vs 4%), pneumonia (10% vs 8%), headache (10% vs 5%), pyrexia (7% vs 5%), vomiting (7% vs 4%), rash (6% vs 2%), decreased weight (6% vs 1%), change in sputum (5% vs 1%), and chest discomfort (5% vs 3%).

**Drug Interactions**: Avoid concomitant use of ARIKAYCE with medications associated with neurotoxicity, nephrotoxicity, and ototoxicity. Some diuretics can enhance aminoglycoside toxicity by altering aminoglycoside concentrations in serum and tissue. Avoid concomitant use of ARIKAYCE with ethacrynic acid, furosemide, urea, or intravenous mannitol.

**Overdosage**: Adverse reactions specifically associated with overdose of ARIKAYCE have not been identified. Acute toxicity should be treated with immediate withdrawal of ARIKAYCE, and baseline tests of renal function should be undertaken. Hemodialysis may be helpful in removing amikacin from the body. In all cases of suspected overdosage, physicians should contact the Regional Poison Control Center for information about effective treatment.

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#### U.S. INDICATION
LIMITED POPULATION: ARIKAYCE<sup>®</sup> is indicated in adults, who have limited or no alternative treatment options, for the treatment of *Mycobacterium avium* complex (MAC) lung disease as part of a combination antibacterial drug regimen in patients who do not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. As only limited clinical safety and effectiveness data for ARIKAYCE are currently available, reserve ARIKAYCE for use in adults who have limited or no alternative treatment options*.* This drug is indicated for use in a limited and specific population of patients.

**This indication is approved under accelerated approval based on achieving sputum culture conversion (defined as 3 consecutive negative monthly sputum cultures) by Month 6. Clinical benefit has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials*.***

**<u>Limitation of Use</u>:** ARIKAYCE has only been studied in patients with refractory MAC lung disease defined as patients who did not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. The use of ARIKAYCE is not recommended for patients with non-refractory MAC lung disease.

Patients are encouraged to report negative side effects of prescription drugs to the FDA. Visit <u>**www.fda.gov/medwatch**</u>, or call 1-800-FDA-1088. You can also call the Company at 1-844-4-INSMED.

#### Please see Full Prescribing Information .

#### About Insmed

Insmed Incorporated is a global biopharmaceutical company on a mission to transform the lives of patients with serious and rare diseases. Insmed's first commercial product is a first-in-disease therapy approved in the United States, Europe, and Japan to treat a chronic, debilitating lung disease. The Company is also progressing a robust pipeline of investigational therapies targeting areas of serious unmet need, including neutrophil-mediated inflammatory diseases and rare pulmonary disorders. Insmed is headquartered in Bridgewater, New Jersey, with a footprint across Europe and in Japan. For more information, visit <u>www.insmed.com</u>.

#### Forward-looking Statements
This press release contains forward-looking statements that involve substantial risks and uncertainties. "Forward-looking statements," as that term is defined in the Private Securities Litigation Reform Act of 1995, are statements that are not historical facts and involve a number of 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 or circumstances) may identify forward-looking statements.

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The forward-looking statements in this press release are based upon the Company's current expectations and beliefs, and involve known and unknown risks, uncertainties and other factors, which may cause the Company's actual results, performance and achievements and the timing of certain events to differ materially from the results, performance, achievements or timings discussed, projected, anticipated or indicated in any forward-looking statements. Such risks, uncertainties and other factors include, among others, the following: failure to obtain, or delays in obtaining, regulatory approvals for ARIKAYCE outside the U.S., Europe or Japan, or for the Company's product candidates in the U.S., Europe, Japan or other markets, including separate regulatory approval for the Lamira<sup>®</sup> Nebulizer System and other product candidate devices in each market and for each usage; failure to successfully commercialize ARIKAYCE, the Company's only approved product, in the U.S., Europe or Japan (amikacin liposome inhalation suspension, Liposomal 590 mg Nebuliser Dispersion, and amikacin sulfate inhalation drug product, respectively), or to maintain U.S., European or Japanese approval for ARIKAYCE; business or economic disruptions due to catastrophes or other events, including natural disasters or public health crises; impact of the COVID-19 pandemic and efforts to reduce its spread on the Company's business, employees, including key personnel, patients, partners and suppliers; risk that brensocatib does not prove effective or safe for patients in ongoing and future clinical studies, including the ASPEN study; risk that TPIP does not prove to be effective or safe for patients in ongoing and future clinical studies; uncertainties in the degree of market acceptance of ARIKAYCE by physicians, patients, third-party payors and others in the healthcare community; the Company's inability to obtain full approval of ARIKAYCE from the U.S. Food and Drug Administration, including the risk that the Company will not successfully or in a timely manner complete the study to validate a patient reported outcome tool and the confirmatory post-marketing clinical trial required for full approval of ARIKAYCE; inability of the Company, PARI or the Company's other third-party manufacturers to comply with regulatory requirements related to ARIKAYCE or the Lamira<sup>®</sup> Nebulizer System; the Company's 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 or the Company's product candidates; inaccuracies in the Company's estimates of the size of the potential markets for ARIKAYCE, brensocatib, TPIP or the Company's other product candidates or in data the Company has used to identify physicians, expected rates of patient uptake, duration of expected treatment, or expected patient adherence or discontinuation rates; the risks and uncertainties associated with, and the perceived benefits of, our secured senior loan with certain funds managed by Pharmakon Advisors, LP and our royalty financing with OrbiMed Royalty & Credit Opportunities IV, LP, including our ability to maintain compliance with the covenants in the agreements for the senior secured loan and royalty financing and the perceived impact of the restrictions on our operations under these agreements; the Company's inability to create an effective direct sales and marketing infrastructure or to partner with third parties that offer such an infrastructure for distribution of ARIKAYCE or any of the Company's product candidates that are approved in the future; failure to obtain regulatory approval to expand ARIKAYCE's indication to a broader patient population; risk that the Company's competitors may obtain orphan drug exclusivity for a product that is essentially the same as a product the Company is developing for a particular indication; failure to successfully predict the time and cost of development, regulatory approval and commercialization for novel gene therapy products; failure to successfully conduct future clinical trials for ARIKAYCE, brensocatib, TPIP and the Company's other product candidates due to the Company's limited experience in conducting preclinical development activities and clinical trials necessary for regulatory approval and its potential inability to enroll or retain sufficient patients to conduct and complete the trials or generate data necessary for regulatory approval, among other things; risks that the Company's clinical studies will be delayed or that serious side effects will be identified during drug development; failure of third parties on which the Company is dependent to manufacture sufficient quantities of ARIKAYCE or the Company's product candidates for commercial or clinical needs, to conduct the Company's clinical trials, or to comply with the Company's agreements or laws and regulations that impact the Company's business or agreements with the Company; the Company's inability to attract and retain key personnel or to effectively manage the Company's growth; the Company's inability to successfully integrate its recent acquisitions and appropriately manage the amount of management's time and attention devoted to integration activities; risks that the Company's acquired technologies, products and product candidates are not commercially successful; the Company's inability to adapt to its highly competitive and changing environment; risk that the Company is unable to maintain its significant customers; risk that government healthcare reform materially increases the Company's costs and damages its financial condition; the Company's inability to adequately protect its intellectual property rights or prevent disclosure of its trade secrets and other proprietary information and costs associated with litigation or other proceedings related to such matters; restrictions or other obligations imposed on the Company by agreements related to ARIKAYCE or the Company's product candidates, including its license agreements with PARI and AstraZeneca AB, and failure of the Company to comply with its obligations under such agreements; the cost and potential reputational damage resulting from litigation to which the Company is or may become a party, including product liability claims; risk that the Company's operations are subject to a material disruption in the event of a cybersecurity attack or issue; business disruptions or expenses related to the upgrade to the Company's enterprise resource planning system; the Company's limited experience operating internationally; changes in laws and regulations applicable to the Company's business, including any pricing reform, and failure to comply with such laws and regulations; the Company's history of operating losses, and the possibility that the Company may never achieve or maintain profitability; goodwill impairment charges affecting the Company's results of operations and financial condition; inability to repay the Company's existing indebtedness and uncertainties with respect to the Company's ability to access future capital; and delays in the execution of plans to build out an additional third-party manufacturing facility approved by the appropriate regulatory authorities and unexpected expenses associated with those plans.

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The Company may not actually achieve the results, plans, intentions or expectations indicated by the Company's forward-looking statements because, by their nature, forward-looking statements involve risks and uncertainties because they relate to events and depend on circumstances that may or may not occur in the future. For additional information about the risks and uncertainties that may affect the Company's business, please see the factors discussed in Item 1A, "Risk Factors," in the Company's Annual Report on Form 10-K for the year ended December 31, 2021 and any subsequent Company filings with the Securities and Exchange Commission (SEC).

The Company cautions readers not to place undue reliance on any such forward-looking statements, which speak only as of the date of this press release. The Company disclaims any obligation, except as specifically required by law and the rules of the SEC, to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements.

#### Contact:

Investors:

Eleanor Barisser

Associate Director, Investor Relations

Insmed

(718) 594-5332

<u>eleanor.barisser@insmed.com</u>

Media:

Mandy Fahey

Executive Director, Corporate Communications

Insmed

(732) 718-3621

amanda.fahey@insmed.com

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## Exhibit 99.2

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**Exhibit 99.2**<br>

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<br> **![](brhc10046302_99-2slide1.jpg)

Investor Presentation January 2023

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![](brhc10046302_99-2slide2.jpg)

Forward Looking Statement Forward Looking Statements This presentation contains forward-looking statements that involve substantial risks and uncertainties. "Forward-looking statements," as that term is defined in the Private Securities Litigation Reform Act of 1995, are statements that are not historical facts and involve a number of 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 or circumstances) may identify forward-looking statements. The forward-looking statements in this presentation are based upon the Company's current expectations and beliefs, and involve known and unknown risks, uncertainties and other factors, which may cause the Company's actual results, performance and achievements and the timing of certain events to differ materially from the results, performance, achievements or timings discussed, projected, anticipated or indicated in any forward-looking statements. Such risks, uncertainties and other factors include, among others, the following: failure to obtain, or delays in obtaining, regulatory approvals for ARIKAYCE outside the U.S., Europe or Japan, or for the Company's product candidates in the U.S., Europe, Japan or other markets, including separate regulatory approval for the Lamira® Nebulizer System and other product candidate devices in each market and for each usage; failure to successfully commercialize ARIKAYCE, the Company's only approved product, in the U.S., Europe or Japan (amikacin liposome inhalation suspension, Liposomal 590 mg Nebuliser Dispersion, and amikacin sulfate inhalation drug product, respectively), or to maintain U.S., European or Japanese approval for ARIKAYCE; business or economic disruptions due to catastrophes or other events, including natural disasters or public health crises; impact of the COVID-19 pandemic and efforts to reduce its spread on the Company's business, employees, including key personnel, patients, partners and suppliers; risk that brensocatib does not prove effective or safe for patients in ongoing and future clinical studies, including the ASPEN study; risk that TPIP does not prove to be effective or safe for patients in ongoing and future clinical studies; uncertainties in the degree of market acceptance of ARIKAYCE by physicians, patients, third-party payors and others in the healthcare community; the Company's inability to obtain full approval of ARIKAYCE from the U.S. Food and Drug Administration, including the risk that the Company will not successfully or in a timely manner complete the study to validate a patient reported outcome tool and the confirmatory post-marketing clinical trial required for full approval of ARIKAYCE; inability of the Company, PARI or the Company's other third-party manufacturers to comply with regulatory requirements related to ARIKAYCE or the Lamira® Nebulizer System; the Company's 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 or the Company's product candidates; inaccuracies in the Company's estimates of the size of the potential markets for ARIKAYCE, brensocatib, TPIP or the Company's other product candidates or in data the Company has used to identify physicians, expected rates of patient uptake, duration of expected treatment, or expected patient adherence or discontinuation rates; the risks and uncertainties associated with, and the perceived benefits of, our secured senior loan with certain funds managed by Pharmakon Advisors, LP and our royalty financing with OrbiMed Royalty & Credit Opportunities IV, LP, including our ability to maintain compliance with the covenants in the agreements for the senior secured loan and royalty financing and the perceived impact of the restrictions on our operations under these agreements; the Company's inability to create an effective direct sales and marketing infrastructure or to partner with third parties that offer such an infrastructure for distribution of ARIKAYCE or any of the Company's product candidates that are approved in the future; failure to obtain regulatory approval to expand ARIKAYCE's indication to a broader patient population; risk that the Company's competitors may obtain orphan drug exclusivity for a product that is essentially the same as a product the Company is developing for a particular indication; failure to successfully predict the time and cost of development, regulatory approval and commercialization for novel gene therapy products; failure to successfully conduct future clinical trials for ARIKAYCE, brensocatib, TPIP and the Company's other product candidates due to the Company's limited experience in conducting preclinical development activities and clinical trials necessary for regulatory approval and its potential inability to enroll or retain sufficient patients to conduct and complete the trials or generate data necessary for regulatory approval, among other things; risks that the Company's clinical studies will be delayed or that serious side effects will be identified during drug development; failure of third parties on which the Company is dependent to manufacture sufficient quantities of ARIKAYCE or the Company's product candidates for commercial or clinical needs, to conduct the Company's clinical trials, or to comply with the Company's agreements or laws and regulations that impact the Company's business or agreements with the Company; the Company's inability to attract and retain key personnel or to effectively manage the Company's growth; the Company's inability to successfully integrate its recent acquisitions and appropriately manage the amount of management's time and attention devoted to integration activities; risks that the Company's acquired technologies, products and product candidates are not commercially successful; the Company's inability to adapt to its highly competitive and changing environment; risk that the Company is unable to maintain its significant customers; risk that government healthcare reform materially increases the Company's costs and damages its financial condition; the Company's inability to adequately protect its intellectual property rights or prevent disclosure of its trade secrets and other proprietary information and costs associated with litigation or other proceedings related to such matters; restrictions or other obligations imposed on the Company by agreements related to ARIKAYCE or the Company's product candidates, including its license agreements with PARI and AstraZeneca AB, and failure of the Company to comply with its obligations under such agreements; the cost and potential reputational damage resulting from litigation to which the Company is or may become a party, including product liability claims; risk that the Company's operations are subject to a material disruption in the event of a cybersecurity attack or issue; business disruptions or expenses related to the upgrade to the Company's enterprise resource planning system; the Company's limited experience operating internationally; changes in laws and regulations applicable to the Company's business, including any pricing reform, and failure to comply with such laws and regulations; the Company's history of operating losses, and the possibility that the Company may never achieve or maintain profitability; goodwill impairment charges affecting the Company's results of operations and financial condition; inability to repay the Company's existing indebtedness and uncertainties with respect to the Company's ability to access future capital; and delays in the execution of plans to build out an additional third-party manufacturing facility approved by the appropriate regulatory authorities and unexpected expenses associated with those plans. The Company may not actually achieve the results, plans, intentions or expectations indicated by the Company's forward-looking statements because, by their nature, forward-looking statements involve risks and uncertainties because they relate to events and depend on circumstances that may or may not occur in the future. For additional information about the risks and uncertainties that may affect the Company's business, please see the factors discussed in Item 1A, "Risk Factors," in the Company's Annual Report on Form 10-K for the year ended December 31, 2021 and any subsequent Company filings with the Securities and Exchange Commission (SEC). The Company cautions readers not to place undue reliance on any such forward-looking statements, which speak only as of the date of this presentation. The Company disclaims any obligation, except as specifically required by law and the rules of the SEC, to publicly update or revise any such statements to reflect any change in expectations or in events, conditions or circumstances on which any such statements may be based, or that may affect the likelihood that actual results will differ from those set forth in the forward-looking statements.

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![](brhc10046302_99-2slide3.jpg)

Build a sustainable biotechnology company by leveraging revenue generation from a portfolio of life-altering therapies for small patient populations experiencing big health problems 5-YEAR VISION

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![](brhc10046302_99-2slide4.jpg)

The next 18 months will be the most transformative in the company's history… CASH > $1 billion to support near-term inflection points COMMERCIAL ENGINE On track to achieve 30% revenue growth in 2022 $285M to $300M in revenue expected in 2023 MATURING PIPELINEClinical data from each of our programs throughout 2023-2024 This is the year you want to build a position in Insmed. 4

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![](brhc10046302_99-2slide5.jpg)

Building sustainable growth by 2025 Commercial 1 2 3 4 ARIKAYCE Brensocatib TPIP\* Early-Stage Research Refractory MAC lung disease Frontline MAClung disease Next Gen Manufacturing Additional Technologies Phase 3 <20% OF EXPENDITURES Phase 2 Preclinical Bronchiectasis Pulmonary hypertension associated with interstitial lung disease (PH-ILD) Pulmonary arterial hypertension (PAH) Musculoskeletal CNS Ocular Rheumatologic >80% OF EXPENDITURES Chronic Rhinosinusitis without Nasal Polyps (CRSsNP) Cystic Fibrosis Hidradenitis Suppurativa (HS) U.S., Japan, EU† Market U.S., Japan, EU† Market U.S., Japan, EU† Market U.S., Japan, EU† Market † European 5 comprised of France, Germany, Italy, Spain and the United Kingdom\*Treprostinil Palmitil Inhalation Powder 5

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![](brhc10046302_99-2slide6.jpg)

1 ARIKAYCE ARIKAYCE is poised to address the front-line population…. First in diseaseapproved product Strongly recommendedfor use in international guidelines Extremely successful commercial launch US/Japan/EU 1st of 2 Phase 3 trials for frontline fully enrolled with topline results Q3 2023 12K-17K (2019E)\* 95-115K (2019E)\* U.S. Refractory MAC lung disease DiagnosedNTMPatients 15K-18K (2018E)\* 125-145K (2018E)\* Japan 1,400 (2018E)\* 14K (2018E)\* EU† Market 2 Brensocatib 3 TPIP 4 Early-Stage Research \*Source: Internal analysis of published NTM epidemiology, primary market research with treating HCPs, and anonymized patient level claims data in US †European 5 comprised of France, Germany, Italy, Spain and the United Kingdom

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![](brhc10046302_99-2slide7.jpg)

Brensocatib – A pipeline in a product Phase 3 data expected 2Q 2024 Blockbuster potential 2 Brensocatib 1 ARIKAYCE 3 TPIP 4 Early-Stage Research First-in-mechanism Potentially first-in-disease in both bronchiectasis and CRSsNP Phase 2 WILLOW data published in NEJM Phase 3 ASPEN trial reads out in just over a year… 1Assumes indication for non-cystic fibrosis bronchiectasis and approval in US, Europe5, and Japan; 2Weycker, et al. Prevalence and incidence of NCFBE among US adults in 2013. Chronic Respiratory Disease. 2017; 3Insmed: Patient Level Claims Data Analysis and Internal Market Research; \*Ex-US estimates based on published epidemiology research, Insmed market research, and extrapolation of US-focused claims and epi data analysis (sourced from swoop/ipm.ai); †European 5 comprised of France, Germany, Italy, Spain and the United Kingdom † ~450K2,3 U.S. ~150K Japan\* ~400K EU† Market\* ~1M TOTAL DIAGNOSED NON-CF BRONCHIECTASIS PATIENTS AT LAUNCH1

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![](brhc10046302_99-2slide8.jpg)

Brensocatib (DPP1 Inhibitor) has potential in a broad range of neutrophil-mediated diseases Neutrophils play an essential role in pathogen destruction and inflammatory mediation. Neutrophils contain the NSPs that have been implicated in a variety of inflammatory diseases such as bronchiectasis, CRS, CF and HS DPP1 catalyzes activation of NSPs Brensocatib shows inhibition of NSPs in multiple clinical studies Phase 2 data published in NEJM showed potential clinical benefits of directly reducing neutrophil-mediated inflammation

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![](brhc10046302_99-2slide9.jpg)

CF Phase 2 Topline Data: Dose & Exposure Dependent Inhibition of Blood NSPs was Observed Cathepsin-G (CatG) Proteinase 3 (Pr3) Neutrophil Elastase (NE) 10 mg 25 mg DOSE 40 mg placebo -14.7% 33.2% 54.9% 74.0% 11.3% 69.5% 86.9% 95.6% 2.5% 15.8% 37.2% 55.0% NSP activity reduction relative to baseline on Day 29 (median): Insmed Dataset: Nov 23, 2022 PK-NSP Relationships FINDINGS Measured NSP data were highly variable within and between subjects Average inhibition on NSP activity was dose dependent, and the degree of inhibition appeared to be CatG > NE > Pr3 Brensocatib demonstrated inhibition of all 3 NSPs especially at the 25 and 40 mg dose levels Clear correlations between NSP activity and brensocatib exposure (Cmax, AUC, trough concentration) or dose were observed The Company concluded that an additional cohort evaluating a 65 mg dose of brensocatib is not needed in this patient population. Ecmax (%inh) Steady-state Exposure 9

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![](brhc10046302_99-2slide10.jpg)

Brensocatib inhibited the NE activity in a dose dependent fashion in all populations tested Blood/Plasma NE Data Comparison Between Studies AstraZeneca Phase 1 Healthy Volunteers (D6190C00001\*\*\*) Insmed NCFBE (WILLOW) Insmed CF\*\*(INS1007-211) 10 mg 25 mg DOSE 40 mg placebo -14.7% 33.2% 54.9% 74.0% 16.5% 34.8% 42.6% 55.1% 3.40% 30.9% 66.5% NA NE activity reduction relative to baseline (median) at 4 week\* in Different Populations: \* Day 29 data for INS1007-211 and INS1007-201, and Day 28 data for D6190C00001 \*\*INS1007-211 PD Dataset: Nov 23, 2022 \*\*\* AZ Study; NE activity was normalized by ANC FINDINGS NE Inhibition in CF subjects was comparable to that in non-CF subjects The degree of NE activity inhibition at Week 4 was generally comparable between CF and non-CF populations 10 Insmed Dataset: Nov 23, 2022

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![](brhc10046302_99-2slide11.jpg)

CF Phase 2 Topline Data: Brensocatib was well-toleratedwith no new safety signals detected FINDINGS Thirteen participants in brensocatib arms and two in placebo reported 43 TEAEs One reported SAE of pulmonary exacerbation in brensocatib 40 mg arm (not related). Four TEAEs were related to study drug (3 in brensocatib and 1 in placebo arms). There were no deaths nor AESIs. 25 mg QD n: 8 (%) AE 40 mg QD n: 8 (%) AE 10 mg QD n: 8 (%) AE TEAE related to study treatment Serious TEAE DOSE Serious TEAE related to study treatment Any TEAE n: 5 (%) AE 29 (%) AE 4 (50) 9 1 (12.5) 21 1 (12.5) 13 0 Brensocatib N:24 Pooled Placebo Total TEAE of Special Interest TEAE related to COVID-194 TEAE resulting in Death 0 0 0 1 (12.5) 1 TEAE leading to study withdrawal 5 (62.5) 11 1 (12.5) 1 0 0 0 0 0 1 (12.5) 24 4 (50) 11 0 0 0 0 0 0 0 2 (40) 5 1 (20) 12 0 0 0 0 0 0 15 (51) 43 3 (10.3) 4 1 (3.4) 1 0 0 0 0 2 (6.9) 34 1Abdominal pain (temporal association), mild (3 event 2 participants) 2Chromaturia (temporal association), mild 3Pulmonary exacerbation 4Includes an TEAE of "fatigue" related to COVID-19 11 Insmed Dataset: Nov 23, 2022

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![](brhc10046302_99-2slide12.jpg)

The potential addressable markets available to be treated via the MOA are enormous CRSsNP ~400K4,5,6,7 Addressable Patients WW (Severe Population) No approved treatments ~70M patients with CRSsNP1, yet many do not respond to corticosteroids and/or Endoscopic Sinus Surgery (ESS) Cystic Fibrosis ~70K8,9 Total WW Diagnosed Patients No approved anti-inflammatory treatments targeting neutrophil-mediated inflammation, the key driver of exacerbations and disease progression HS~100K Moderate to Severe Patients in US10,11 Current approaches represent significant burden for patients who require multiple therapies and/or surgery to manage disease Bronchiectasis Up to 6.7M Additional Patients WW Beyond Launch Focus No approved treatments ~1.7M undiagnosed BE patients/misdiagnosed with COPD or asthma1,2 + ~2.3M to 5M undiagnosed BE patients/co-morbid with COPD2,3 1Potential Undiagnosed or Misdiagnosed (with COPD, Asthma) BE patients in US estimated based on Medical Experts driven insights applied to patient level claims data using advanced analytics / statistical methods; 2Ex-US estimates based on published epidemiology research, Insmed market research, and extrapolation of US-focused claims and epi data analysis (sourced from swoop/ipm.ai); 3Potential Undiagnosed or Co-morbid (with COPD) BE patients in US derived based on internal Insmed meta-analysis of 16 epi studies that look at BE prevalence in COPD patients; 4Cho et. al, Chronic Rhinosinusitis without Nasal Polyps J Allergy Clin Immunol Pract. 2016 ; 4(4): 575–582. doi:10.1016/j.jaip.2016.04.015; 5Benjamin et. al, Clinical Characteristics of Patients with Chronic Rhinosinusitis without Nasal Polyps in an Academic Setting, J ALLERGY CLIN IMMUNOL PRACT VOLUME 7, NUMBER 3, MARCH 2019; 6Patient level claims data analysis US ONLY (Komodo Health), proportion of actively managed CRS patients with no Dx codes for Nasal Polyps in patient history; Extrapolated to Europe5 and Japan; 7Patient level claims data analysis US ONLY (Komodo Health), proportion of actively managed CRSsNP patients with ESS; Extrapolated to Europe5 and Japan; 8CF Foundation, https://www.cff.org/intro-cf/about-cystic-fibrosis; 9Cystic Fibrosis Journal, https://www.cysticfibrosisjournal.com/action/showFullTableHTML?isHtml=true&tableId=t0015&pii=S1569-1993%2816%2930655-5; 10Phan et al, Global prevalence of hidradenitis suppurativa and geographical variation—systematic review and metaanalysis Biomedical Dermatology (2020) 4:2; 11Puri, Ajay: Hidradenitis Suppurativa Executive Insights, DRG Nov 2019 \*Hidradenitis Suppurativa

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![](brhc10046302_99-2slide13.jpg)

First two pillars will transform Insmed, as we grow to address patient populations from tens of thousands to more than 1 million patients … with potentially more beyond Potential Addressable Patient Populations Refractory NTM NTM + All Bronchiectasis + Additional Indications Refractory + Frontline MAC NTM + Bronchiectasis at Launch BRENSOCATIB ARIKAYCE CRSsNP CF Additional BE BE Frontline MAC NTM Refractory MAC NTM 2023 Revenue guidance of $285M to $300M for Refractory NTM Number of Patients

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![](brhc10046302_99-2slide14.jpg)

"We strongly believe that TPIP has the potential to be the best-in-class prostanoid therapy…" – KOL at December 2022 Ad Board meeting Designed to harness full potential of prostanoid therapy Phase 1 demonstrated dosing >600 mcg Achieved 16 weeks of treatment in a PAH patient at 320 mcg in Phase 2a Phase 2 in PH-ILD and Phase 2b in PAH are both underway U.S. Diagnosed patients with PH-ILD Diagnosed patients with PAH ~7K1,2,3,6 ~4K7-~6K8 Japan ~45K1,2,3 ~35K4,5 ~60K1,2,3,9 ~40K10,11,12,13 EU† Market 2 Brensocatib 3 TPIP 1 ARIKAYCE 4 Early-Stage Research †European 5 comprised of France, Germany, Italy, Spain and the United Kingdom; 1Coultas DB et al, "The epidemiology of interstitial diseases", Am J Repir Crit Care Med, 1994; 2Ryu et al., "Pulmonary hypertension in patients with interstitial lung disease." Mayo Clinic Proceedings, 2007; 3Anderson et al., "Pulmonary hypertension in interstitial lung disease: prevalence, prognosis and 6 min walk test." Respir Med, 2012; 4Kirson N et al, "Prevalence of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension in the United States", Jul 2011; 5Analysis of Compile Health claims; 6Meta-analysis of several Japan-based publications relating to interstitial lung diseases; 7Japan's Intractable Disease Database; 8Insmed Primary Quantitative Market Research Fielded September 2021; 9Duchemann et al., "Prevalence and incidence of interstitial lung diseases in a multi-ethnic county of Greater Paris." European Respiratory Journal, 2017; 102019 National Audit of Pulmonary Hypertension Great Britain; 11Humbert M et al, "Pulmonary arterial hypertension in France: results from a national registry", Feb 2006; 12Hoeper M et al, "Incidence and prevalence of pulmonary arterial hypertension in Germany", Nov 2015; 13Escribano-Subias P et al, "Survival in pulmonary hypertension in Spain: insights from the Spanish registry", 2012

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![](brhc10046302_99-2slide21.jpg)

We designed TPIP to chemically accomplish the continuous delivery of a prostanoid and its demonstrated benefits … aerosol delivery of the drug had a much greater vasodilatory effect than intravenous delivery. At the highest dose, aerosol delivery of the drug returned both pulmonary vascular resistance and pulmonary artery pressure to baseline levels… " " Ongoing Phase 2 trials designed to validate this potential benefit 15 Inhalation delivery of a prostanoid is more potent than systemic delivery Sheep Model of Sustained Acute Pulmonary Hypertension

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![](brhc10046302_99-2slide16.jpg)

<20% of expenditures Each modality offers a distinct advantage INITIAL INDICATIONS Musculoskeletal, CNS, Ocular, Rheumatologic 3 TPIP Early-Stage Research: A technology platform that can deliver impactful therapies in potentially less time, at less cost 4 Early-Stage Research 2 Brensocatib 1 ARIKAYCE AI-driven protein engineering Gene Therapy Protein manufacturing BUILDING A ROBUST PIPELINE Increased safety with decreased viral load lower costs with higher yields

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![](brhc10046302_99-2slide17.jpg)

Our three distinct research engines are expected to generate ≥6 INDs/Phase 1 studies by year-end 2025 Chemistry, Formulation & Delivery Gene Therapy, Novel Protein Manufacturing AI-Driven Protein Engineering Therapeutic Targets Location Team size Leadership Rheumatology Immunology Improved Viral Capsids Next-generation DPP1 inhibitor Musculoskeletal – 1H23 (IND) CNS – Late '23 / Early '24 (IND) New Jersey New Hampshire California N ~40 N ~15 N ~35 Karl Griswold Biologics & NH Site Lead Chris Bailey-KelloggComputational Biology Walter Perkins Chief Technology Officer Brian Kaspar Chief Scientific Officer

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![](brhc10046302_99-2slide18.jpg)

Significant data readouts across the next 18 months 1H 2023 1 2 3 ARIKAYCE Brensocatib TPIP 2H 2023 1H 2024 Musculoskeletal preclinical data (2Q) CNS preclinical data (2Q) Cystic Fibrosis PK/PD Data (1Q) ARISE Topline Results (3Q) Interim dose titration safety & tolerability levels PH-ILD Topline Results Musculoskeletal Clinical data ASPEN Topline Results (2Q) 4 Early-Stage Research

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![](brhc10046302_99-2slide19.jpg)

Our strategy reflects our commitment to patients — to deliver life-altering therapies and to work quickly and creatively to deliver meaningful results Life-transforming innovation happens at theconvergence of breakthrough science and collaborative culture #1 on Science's 2022 Top Biopharma Employers List (2 YEARS IN A ROW!) 700+ employees across the world 19

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![](brhc10046302_99-2slide20.jpg)

Driving our Transformation INSMED'S MISSONTo deliver life-altering therapies to small patient populations experiencing big health problems MATURING PIPELINE multiple milestones 2023-2024 OUR STRATEGY leverage revenue generation to create a sustainable biotechnology company… CASH > $1 billon to support near-term inflection points COMMERCIAL ENGINE $285M to $300M in revenue expected in 2023

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