MannKind Reports Positive Phase 1b Results for Inhaled Nintedanib Therapy in Idiopathic Pulmonary Fibrosis

Study Shows Favorable Safety Profile for Inhaled Nintedanib in IPF Patients

MannKind Corporation has announced positive topline results from its Phase 1b INFLO-1 clinical trial evaluating nintedanib dry powder inhalation (DPI) in patients with idiopathic pulmonary fibrosis (IPF).

The study achieved its primary objective by showing that inhaled nintedanib was generally safe and well tolerated in people living with IPF. These findings support the continued development of the company's inhaled treatment as it moves into Phase 2 clinical testing.

The Phase 1b trial enrolled 27 patients across 10 clinical sites in the United States. Researchers tested two multiple-ascending dose regimens of nintedanib DPI over a seven-day treatment period.

Understanding Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis is a chronic lung disease that causes permanent scarring of lung tissue. As the disease progresses, the lungs become less able to deliver oxygen throughout the body, making it increasingly difficult for patients to breathe.

Although treatments are available, IPF continues to have high rates of illness and death. Current therapies help slow disease progression, but many patients still struggle with treatment-related side effects.

According to the American Lung Association and GlobalData, around 100,000 people in the United States are living with IPF. Globally, the disease affects an estimated 1 to 1.5 million people.

What Is Nintedanib Dry Powder Inhalation?

Nintedanib is already approved as an oral medicine for treating idiopathic pulmonary fibrosis. While it helps slow the progression of the disease, oral treatment can cause side effects such as diarrhoea, nausea, and vomiting, making long-term treatment difficult for some patients.

MannKind's investigational therapy, known as MNKD-201, delivers nintedanib directly into the lungs using the company's Technosphere dry powder inhalation technology.

The goal is to deliver higher drug concentrations directly to the lungs while reducing exposure throughout the rest of the body. This approach may lower the risk of systemic side effects and improve treatment tolerability.

Phase 1b Study Met Its Primary Goal

The INFLO-1 study successfully met its primary objective of evaluating the safety, tolerability, and pharmacokinetics of inhaled nintedanib.

Researchers found that patients generally tolerated the treatment well, with no major safety concerns reported during the study.

The positive results provide additional support for advancing the program into larger clinical studies.

Key Safety Findings

The study reported several encouraging safety outcomes.

Researchers observed:

• No serious adverse events during the trial.
• No drug-related gastrointestinal side effects such as diarrhoea, nausea, or vomiting.
• No bronchospasm events.
• No treatment discontinuations.
• No dose reductions.
• No meaningful differences in lung function tests compared with placebo.

These findings suggest that inhaled nintedanib may avoid some of the common side effects associated with the currently available oral therapy.

Most Patients Experienced Little or No Cough

One concern with inhaled therapies is whether they trigger coughing during treatment.

In the INFLO-1 study, most patients did not experience cough. When cough was reported, it was generally mild, short-lived, and resolved without additional treatment.

Importantly, no patients stopped treatment or required dose reductions because of coughing.

Findings Build on Earlier Phase 1a Results

The latest results also strengthen the safety findings previously seen in MannKind's completed Phase 1a study involving healthy volunteers.

That earlier study also demonstrated favorable safety and tolerability with:

• No serious adverse events.
• No treatment discontinuations.
• No significant safety signals.

Pharmacokinetic data from the Phase 1a trial also showed rapid drug absorption and dose-proportional increases in blood concentrations, supporting effective deep-lung delivery through inhalation.

Largest Clinical Experience with Inhaled Nintedanib in IPF

Across the completed Phase 1a and Phase 1b clinical studies, 48 individuals have now received inhaled nintedanib.

This includes 18 patients living with idiopathic pulmonary fibrosis, making it the largest reported clinical dataset evaluating an inhaled form of nintedanib in IPF patients to date.

The growing clinical experience continues to support further development of the therapy.

CEO Highlights Progress of the Program

Michael Castagna, PharmD, Chief Executive Officer of MannKind Corporation, said the latest results represent an important milestone for the company's pulmonary fibrosis program.

He noted that participants have now received more than 700 inhalations across both Phase 1 studies, including nearly 450 inhalations in patients with IPF.

According to Castagna, cough was not a meaningful barrier to treatment, and the favorable safety profile increases confidence as the company advances into Phase 2 development.

Global Phase 2 Study Already Underway

Following the encouraging Phase 1 results, MannKind has already launched its global Phase 2 INFLO-2 clinical trial.

The randomized, double-blind, placebo-controlled study plans to enroll approximately 210 patients across about 85 sites worldwide.

Participants will receive one of two inhaled dosing regimens or placebo for 12 weeks before entering a 24-week open-label extension in which all participants receive active treatment.

What Researchers Will Evaluate in Phase 2

The primary objective of the Phase 2 study is to continue evaluating the safety and tolerability of inhaled nintedanib.

Researchers will also examine several measures that may indicate treatment effectiveness, including:

• Annualized decline in forced vital capacity (FVC), an important measure of lung function.
• Disease progression.
• Pulmonary exacerbations.
• Exercise capacity.
• Patient-reported outcomes.
• Pharmacokinetics.

These results will help determine whether inhaled nintedanib can offer meaningful clinical benefits for people living with idiopathic pulmonary fibrosis.

MannKind Continues Expanding Its Respiratory Pipeline

MannKind Corporation is focused on developing patient-centered therapies for chronic diseases, particularly cardiometabolic conditions and orphan lung diseases.

The company has already commercialized two FDA-approved dry powder inhalation therapies using its Technosphere technology, both demonstrating low discontinuation rates due to cough.

With the successful completion of the Phase 1b INFLO-1 study and the ongoing global Phase 2 INFLO-2 trial, MannKind continues advancing inhaled nintedanib as a potential new treatment option for patients living with idiopathic pulmonary fibrosis.