Insmed Provides Clinical and Business Update (Form 8-K)

Insmed Provides Clinical and Business Update

-Phase 2b BiRCh Study of Brensocatib in CRSsNP Did Not Meet Primary or Secondary Efficacy Endpoints; Safety Consistent with Previous Studies; Insmed Discontinues CRSsNP Program-

-Company Acquires Phase 2 Ready Monoclonal Antibody for Potential Respiratory and Immunological & Inflammatory Indications-

BRIDGEWATER, N.J., December 17, 2025 -- Insmed Incorporated (Nasdaq:INSM), a people-first global biopharmaceutical company striving to deliver first- and best-in-class therapies to transform the lives of patients facing serious diseases, announced today that the Phase 2b BiRCh study of brensocatib in patients with chronic rhinosinusitis without nasal polyps (CRSsNP) did not meet its primary or secondary efficacy endpoints in either the 10 mg or 40 mg treatment arms. Brensocatib was well tolerated, with no new safety signals identified, including in the 40 mg arm, which is the highest dose Insmed has studied to date. Insmed has discontinued its development program of brensocatib in CRSsNP effective immediately and intends to present these data at a future congress.

"Given that there are no animal models in this disease, the purpose of this proof-of-concept study was to determine if brensocatib could provide treatment benefit to patients with CRSsNP," said Martina Flammer, M.D., MBA, Chief Medical Officer of Insmed. "While we are disappointed in the results, they provided us with a clear answer. We extend our sincerest gratitude to the patients and investigators who made the BiRCh study possible."

In the study, a negative score in the primary endpoint of change from baseline to the 28-day average of daily Sinus Total Symptom Score (sTSS) at Week 24 indicated an improvement. Topline results from each treatment arm were as follows: placebo least squares (LS) mean was -2.44; brensocatib 10 mg LS mean was -2.21; and brensocatib 40 mg LS mean was -2.33. Treatment-emergent adverse event (TEAE) percentages were:

Acquisition of Phase 2 Ready Asset: INS1148

Insmed also announced today the acquisition of INS1148, an investigational monoclonal antibody with the potential to be a first-in-class therapy to address respiratory and immunological and inflammatory diseases with high unmet need. Through its novel mechanism of action, INS1148 has the potential to preferentially target a specific isoform of Stem Cell Factor SCF248, which prevents only the inflammatory cascade downstream of c-Kit signaling, while leaving its critical homeostatic and tissue healing pathways intact. Insmed plans to advance Phase 2 development programs for INS1148 initially in interstitial lung disease and moderate-to-severe asthma. INS1148 (formerly known as OpSCF) was developed by Opsidio, a private, clinical-stage company.

Dr. Flammer added, "The acquisition of INS1148 adds a clinical-stage monoclonal antibody with a novel mechanism of action to our growing pipeline. We look forward to advancing this potentially first-in-class therapy in multiple serious diseases."

About the Phase 2b BiRCh Study

The Phase 2b trial of brensocatib in patients with CRSsNP was a randomized, double-blind, parallel-group, placebo-controlled, multicenter study to evaluate the efficacy and safety of brensocatib compared to placebo. The study was conducted at 104 sites globally, and a total of 288 patients were randomized 1:1:1 to receive either brensocatib 10 mg (n=99), brensocatib 40 mg (n=94), or placebo (n=95) daily for 24 weeks in addition to daily treatment with mometasone furoate nasal spray background therapy. The primary endpoint was change from baseline in the 28-day average of daily sTSS at Week 24. Secondary endpoints included changes in percentage of sinus opacification, Sino-Nasal Outcome Test 22 score, modified Lund-MacKay CT score, 28-day average of daily Nasal Congestion score, 28-day average of daily Peak Nasal Inspiratory Flow, as well as proportion of participants requiring rescue therapy and mean brensocatib plasma concentration.

About Insmed

Insmed Incorporated is a people-first global biopharmaceutical company striving to deliver first- and best-in-class therapies to transform the lives of patients facing serious diseases. The Company is advancing a diverse portfolio of approved and mid- to late-stage investigational medicines as well as cutting-edge drug discovery focused on serving patient communities where the need is greatest. Insmed's most advanced programs are in pulmonary and inflammatory conditions, including two approved therapies to treat chronic, debilitating lung diseases. The Company's early-stage programs encompass a wide range of technologies and modalities, including gene therapy, AI-driven protein engineering, protein manufacturing, RNA end-joining, and synthetic rescue.

Headquartered in Bridgewater, New Jersey, Insmed has offices and research locations throughout the United States, Europe, and Japan. Insmed is proud to be recognized as one of the best employers in the biopharmaceutical industry, including spending five consecutive years as the No. 1 Science Top Employer. Visit www.insmed.com to learn more or follow us on LinkedIn, Instagram, YouTube, and X.