MannKind Advances Inhaled Nintedanib into Phase 2 Trial for IPF

MannKind Corporation has achieved two key milestones for MNKD-201, its inhaled nintedanib dry powder inhaler (DPI) therapy for idiopathic pulmonary fibrosis (IPF). The company finalized patient randomization in the U.S.-based Phase 1b INFLO-1 study (NCT07344558) and initiated global enrollment in the Phase 2 INFLO-2 trial, with the first patient enrolled in Windsor, Canada.

These milestones advance the program into mid-stage evaluation as MannKind investigates whether direct pulmonary delivery of nintedanib can improve tolerability while maintaining antifibrotic activity. Data from INFLO-1 are expected in the third quarter of 2026.

Direct Pulmonary Delivery Rationale

IPF is a progressive, fatal lung disease marked by irreversible scarring and declining lung function. Despite available therapies, the disease remains associated with substantial morbidity and mortality. The current treatment landscape is largely dominated by the oral antifibrotic agents nintedanib and pirfenidone, both of which can be limited by tolerability challenges that affect long-term treatment persistence.

Nintedanib, an established oral therapy, reduces lung function decline but is associated with gastrointestinal and other systemic side effects that can impact adherence. MannKind’s MNKD-201 leverages its Technosphere® dry powder inhalation platform to deliver nintedanib directly to the deep lung, with the goal of achieving therapeutic concentrations at the site of disease while limiting systemic exposure.

MannKind’s Technosphere platform already supports two FDA-approved inhaled therapies, with previous clinical experience showing low discontinuation rates related to cough.

Trial Design and Objectives

INFLO-1 is a randomized, double-blind, placebo-controlled Phase 1b study evaluating multiple ascending doses of nintedanib DPI in patients with IPF. Primary objectives include safety, tolerability, and pharmacokinetics compared with placebo. MannKind reports that emerging findings continue to support the safety and tolerability profile of inhaled nintedanib, with detailed data expected later this year.

INFLO-2 will enroll approximately 210 patients across 85 sites worldwide. Patients will be randomized equally across three treatment arms: nintedanib DPI 2 mg four times daily, nintedanib DPI 4 mg twice daily, or placebo for 12 weeks. A 24-week open-label extension will follow, allowing all participants to receive active treatment.

The study’s primary objective is to evaluate safety and tolerability while identifying an optimal dose. Secondary endpoints include annualized decline in forced vital capacity (FVC), disease progression, pulmonary exacerbations, exercise capacity, patient-reported outcomes, and pharmacokinetic measures.

Clinical Implications

Wassim Fares, MD, Senior Vice President and Therapeutic Area Head of Respiratory, said early findings continue to support the hypothesis that inhaled nintedanib may efficiently deliver therapy to the lungs while improving tolerability and treatment adherence. He also highlighted the potential for future combination use alongside existing and emerging IPF therapies.

Chief Executive Officer Michael Castagna described the transition into Phase 2 development as an important milestone for the program. With Phase 1b results anticipated in Q3 2026 and global enrollment now underway, the company is positioned to generate early clinical validation of its inhaled antifibrotic approach and further define its potential role in IPF treatment.

Positive Phase 1b data later this year could provide the first clinical validation of inhaled nintedanib in patients with IPF and help guide dose selection for subsequent stages of development.

Reference

MannKind Enters Data-Rich Development Period with Completion of Randomization in Phase 1b INFLO-1 Study and Enrollment of First Patient in Phase 2 INFLO-2 Trial for Nintedanib DPI in Patients with IPF | MannKind Corporation