On August 5, 2021 Insmed Incorporated (Nasdaq:INSM), a global biopharmaceutical company on a mission to transform the lives of patients with serious and rare diseases, reported financial results for the second quarter ended June 30, 2021 and provided a business update (Press release, Insmed, AUG 5, 2021, View Source [SID1234585806]).

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"Insmed made meaningful progress in the second quarter of 2021, with important achievements across our four pillars—ARIKAYCE, brensocatib, TPIP, and translational medicine," commented Will Lewis, Chair and Chief Executive Officer of Insmed. "With the launch of ARIKAYCE just last month in Japan, the largest market for refractory MAC lung disease that we are pursuing, we’re thrilled that our lead product is now available in three major territories. We continue to enroll patients in both the Phase 3 ASPEN study of brensocatib in patients with bronchiectasis and the ARIKAYCE frontline clinical trial program in patients with NTM lung disease in line with expectations, and we are advancing TPIP to Phase 2 development in both PAH and PH-ILD. As we carry forward learnings from the past year and a half in navigating the pandemic, we have great confidence in our ability to execute on our commercial and clinical activities around the world."

Recent Corporate Developments & Program Highlights

ARIKAYCE

ARIKAYCE launched in Japan in July of 2021, following its approval by the Ministry of Health, Labour, and Welfare in March of 2021 for the treatment of patients with nontuberculous mycobacterial (NTM) lung disease caused by Mycobacterium avium complex (MAC) who did not sufficiently respond to prior treatment with a multidrug regimen. ARIKAYCE has been priced in Japan in line with list prices in the U.S. and Europe.
Insmed continues to advance the European launch of ARIKAYCE following its approval by the European Commission in October of 2020 for the treatment of NTM lung infections caused by MAC in adults with limited treatment options who do not have cystic fibrosis (CF). Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Enrollment continues in the post-approval confirmatory frontline clinical trial program of ARIKAYCE in patients with NTM lung disease caused by MAC. The program consists of ARISE, an interventional study designed to validate a patient-reported outcome (PRO) tool in MAC lung disease, and ENCORE, a pivotal trial designed to establish, using the PRO tool validated in the ARISE trial, the clinical benefits and evaluate the safety of ARIKAYCE in patients with newly diagnosed MAC lung disease.
Brensocatib

Enrollment continues 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. Patients with bronchiectasis due to CF may not be enrolled in the study.
The CF Therapeutics Development Network has endorsed Insmed’s study protocol for brensocatib in CF and the process for initiating study sites for a Phase 2 pharmacokinetic/pharmacodynamic multiple-dose study is now underway.
TPIP

Insmed expects to present data from the Phase 1 healthy volunteer trial of TPIP at the European Society of Cardiology Congress on August 30, 2021. The Company reported positive topline data from this study earlier this year.
Insmed plans to advance two Phase 2 studies of TPIP in patients with pulmonary arterial hypertension (PAH). The first study will measure the impact of TPIP on pulmonary vascular resistance (PVR) over a 24-hour period. The Company anticipates sharing preliminary data from a small number of patients in this study in the second half of 2021. The second study will evaluate the effect of TPIP on PVR and 6-minute walk distance over a 16-week treatment period. The Company plans to initiate this study in the fourth quarter of 2021.
Insmed plans to initiate a Phase 2 study of TPIP in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD) in early 2022.
Corporate Updates

In July of 2021, Insmed announced the promotion of Michael Smith to the role of General Counsel, Senior Vice President of Insmed, replacing Christine Pellizzari, who retired from her position as the Company’s Chief Legal Officer. Mike joined Insmed in 2014 and most recently served as the Company’s Senior Vice President, General Counsel – U.S. In his new role, Mike will have responsibility for Insmed’s global legal function, including corporate governance, intellectual property, and contract management.
Second Quarter 2021 Financial Results

Total revenue for the second quarter ended June 30, 2021 was $45.4 million, compared to total revenue of $42.5 million for the second quarter of 2020.
Cost of product revenues (excluding amortization of intangible assets) was $10.8 million for the second quarter of 2021, compared to $10.0 million for the second quarter of 2020.
Research and development (R&D) expenses were $64.7 million for the second quarter of 2021, compared to $35.7 million for the second quarter of 2020.
Selling, general and administrative (SG&A) expenses for the second quarter of 2021 were $57.2 million, compared to $49.7 million for the second quarter of 2020.
For the second quarter of 2021, Insmed reported a GAAP net loss of $117.3 million, or $1.07 per share, compared to a GAAP net loss of $61.9 million, or $0.64 per share, for the second quarter of 2020.
During the second quarter of 2021, Insmed completed a public offering of 11,500,000 shares of common stock, including 1,500,000 shares issued pursuant to the exercise in full of the underwriters’ option to purchase additional shares, as well as a public offering of $575 million aggregate principal amount of its 0.75% convertible senior notes due 2028 (the 2028 Convertible Notes), including $75 million aggregate principal amount of notes purchased pursuant to the exercise in full of the underwriters’ option to purchase additional notes, solely to cover over-allotments. The offerings resulted in net cash proceeds of approximately $270.1 million and $559.0 million, respectively, after deducting underwriting discounts and other offering-related expenses. A portion of the net cash proceeds from the 2028 Convertible Notes was used to repurchase $225.0 million of the Company’s outstanding 1.75% convertible senior notes due 2025 (2025 Convertible Notes). The offerings resulted in net cash proceeds of approximately $590.0 million after the repurchase of a portion of the outstanding 2025 Convertible Notes.
Balance Sheet and Planned Investments

As of June 30, 2021, Insmed had cash and cash equivalents of $928.3 million. The Company’s total operating expenses for the second quarter of 2021 were $133.9 million. Adjusted R&D expenses for the second quarter of 2021 were $58.9 million and adjusted SG&A expenses for the second quarter of 2021 were $48.8 million. Adjusted R&D expenses and adjusted SG&A expenses are non-GAAP measures, which we describe further below.

The Company plans to continue to invest in the following key activities in 2021:

(i)

U.S. commercialization of ARIKAYCE;

(ii)

clinical trial activities, including (a) advancement of the frontline clinical trial program for ARIKAYCE (ARISE and ENCORE), (b) advancement of the Phase 3 ASPEN study of brensocatib in patients with bronchiectasis, (c) advancement of clinical development of TPIP, and (d) advancement of our translational medicine efforts; and

(iii)

launch activities for ARIKAYCE in initial European countries and in Japan.

Conference Call

Insmed will host a conference call beginning today at 8:30 AM Eastern Time. Shareholders and other interested parties may participate in the conference call by dialing (844) 200-6205 (domestic) or +44-208-0682-558 (international) and referencing access code 711350. The call will also be webcast live on the Company’s website at www.insmed.com.

A replay of the conference call will be accessible approximately 45 minutes after its completion through September 6, 2021 by dialing (929) 458-6194 (domestic) or +44-204-525-0658 (international) and referencing access code 984249. A webcast of the call will also be archived for 90 days under the Investor Relations section of the Company’s website at www.insmed.com.

Non-GAAP Financial Measures

In addition to the U.S. generally accepted accounting principles (GAAP) results, this earnings release includes non-GAAP financial measures: adjusted R&D expenses, which Insmed defines as R&D expenses less stock-based compensation expense and depreciation; and adjusted SG&A expenses, which Insmed defines as SG&A expenses less stock-based compensation and depreciation. A reconciliation of these non-GAAP financial measures to their most directly comparable GAAP financial measure is presented in the table attached to this press release.

Management believes that these non-GAAP financial measures are useful to both management and investors in analyzing our ongoing business and operating performance. Management believes that providing this non-GAAP information to investors, in addition to the GAAP results, allows investors to view our financial results in the way that management views financial results. Management does not intend the presentation of these non-GAAP financial measures to be considered in isolation or as a substitute for results prepared in accordance with GAAP. In addition, these non-GAAP financial measures may differ from similarly named measures used by other companies.

About ARIKAYCE

ARIKAYCE is approved in the United States as ARIKAYCE (amikacin liposome inhalation suspension), in Europe as ARIKAYCE Liposomal 590 mg Nebuliser Dispersion, and in Japan as ARIKAYCE 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 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 Nebulizer System manufactured by PARI Pharma GmbH (PARI).

About PARI Pharma and the Lamira Nebulizer System

ARIKAYCE is delivered by a novel inhalation device, the Lamira Nebulizer System, developed by PARI. Lamira 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.

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 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.

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.

U.S. INDICATION

LIMITED POPULATION: ARIKAYCE 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.

Limitation of Use: 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 www.fda.gov/medwatch, or call 1–800–FDA–1088. You can also call the Company at 1-844-4-INSMED.