MannKind Advances Inhaled Nintedanib with Positive Phase 1b IPF Data

MannKind Corporation has reported positive topline results from the Phase 1b INFLO-1 trial (NCT07344558) evaluating nintedanib dry powder inhalation (DPI; MNKD-201) in patients with idiopathic pulmonary fibrosis (IPF). The randomized, double-blind, placebo-controlled study achieved its primary objective, showing that inhaled nintedanib was generally safe and well tolerated over seven days of treatment without treatment-related serious adverse events or study drug discontinuations.

The findings strengthen the clinical case for inhaled nintedanib as a potential alternative to oral therapy by delivering the antifibrotic agent directly to the lungs while potentially reducing systemic exposure and associated adverse effects.

Inhaled Nintedanib Targets the Lungs Directly

Idiopathic pulmonary fibrosis is a progressive interstitial lung disease characterized by irreversible lung scarring, declining lung function, and high mortality. Oral nintedanib slows disease progression but commonly causes systemic gastrointestinal adverse effects, including diarrhea, nausea, and vomiting, which may limit long-term treatment adherence.

MNKD-201 uses MannKind’s Technosphere® dry powder inhalation platform to deliver nintedanib directly into the deep lung. The localized delivery strategy aims to maintain therapeutic drug concentrations at the site of fibrosis while minimizing systemic exposure that contributes to dose-limiting toxicities.

Phase 1b Trial Demonstrated Favorable Safety and Tolerability

The INFLO-1 study enrolled 27 patients with IPF across 10 U.S. clinical sites and evaluated two multiple-ascending-dose regimens of inhaled nintedanib administered over seven days.

The trial reported

• No serious adverse events
• No bronchospasm events
• No treatment discontinuations or dose reductions
• No drug-related gastrointestinal adverse events, including diarrhea, nausea, or vomiting
• No clinically meaningful differences in spirometry compared with placebo
• Approximately 90% of participants experienced either no cough (60%) or only mild cough (30%), with cough episodes remaining transient and resolving without intervention

Across the study, nearly 450 inhalations were administered to patients with IPF without identifying new safety concerns.

The results build on the previously completed Phase 1a study in healthy volunteers, which also demonstrated favorable safety, good tolerability, and pharmacokinetic findings consistent with rapid deep-lung drug delivery. Together, the Phase 1 program has exposed 48 participants, including 18 patients with IPF, to inhaled nintedanib, representing the largest reported clinical experience with this therapeutic approach in IPF.

Leadership Highlights Clinical Progress

Michael Castagna, PharmD, Chief Executive Officer of MannKind, said the Phase 1b findings further validate the company’s Technosphere inhalation platform for pulmonary fibrosis. He noted that more than 700 total inhalations have now been administered across the Phase 1 program, with cough remaining infrequent, predominantly mild, short-lived, and never leading to treatment discontinuation or dose reduction.

The company believes this safety findings provide increasing confidence as development advances into mid-stage clinical testing.

Global Phase 2 INFLO-2 Trial Continues Enrollment

MannKind is actively enrolling patients into the global Phase 2 INFLO-2 trial, which plans to recruit approximately 210 participants across roughly 85 international sites.

Participants are randomized to receive either 2 mg nintedanib DPI four times daily, 4 mg twice daily, or placebo for 12 weeks, followed by a 24-week open-label extension during which all participants receive active treatment.

The primary endpoint evaluates safety and tolerability, while secondary endpoints include the annualized decline in forced vital capacity (FVC), disease progression, pulmonary exacerbations, exercise capacity, patient-reported outcomes, and pharmacokinetics.

Additional clinical data from INFLO-1 are expected to be presented at a future scientific meeting as development of MNKD-201 progresses through Phase 2 evaluation.

Reference

MannKind Reports Positive Phase 1b INFLO-1 Results, Demonstrating Safety and Tolerability of Nintedanib DPI and Clinical Validation of Its DPI Technology in IPF | MannKind Corporation