MannKind (MNKD) Study result summary

Clinical program overview and study design

• Preclinical studies showed high lung concentrations and minimal systemic exposure, establishing a wide safety margin for nintedanib DPI before human trials.

• Phase 1a and 1b studies in healthy adults and IPF patients demonstrated safety, tolerability, and predictable pharmacokinetics, with no serious adverse events, GI issues, or discontinuations.

• Phase 1b (INFLO-1) was a randomized, double-blind, placebo-controlled study in 27 IPF patients across 10 U.S. sites, using multiple ascending dose regimens over seven days.

• The ongoing global phase II (INFLO-2) will enroll up to 210 IPF patients aged 40-85, evaluating safety, tolerability, and efficacy over a 12-week control period plus a 24-week open-label extension.

• Secondary endpoints in phase II include lung function decline, disease progression, and patient-reported outcomes.

Key safety and tolerability findings

• No serious adverse events, GI burden, bronchospasm, or discontinuations were observed in phase 1b; most patients experienced no or only mild, transient cough.

• Cough was the most common adverse event: 60% had no cough, 30% mild, and 10% moderate, all transient and mostly after the first dose.

• No severe cough, dose reductions, or discontinuations due to cough; no correlation between cough and powder mass.

• No difference in spirometry or pulmonary function between active and placebo groups.

• Safety profile aligns with prior Technosphere platform experience, with <3% discontinuation due to cough in approved products.

Pharmacokinetics and delivery platform

• Technosphere DPI delivers nintedanib efficiently to the deep lung, achieving plasma Cmax 6–8 times higher than nebulized formulations at comparable doses.

• High peak lung concentrations (Cmax) are considered more relevant for anti-fibrotic activity than total exposure (AUC).

• The platform is validated in over 50,000 patients and two FDA-approved products, supporting consistent deep lung delivery and long-term adherence.

• Technosphere particles are well-tolerated, with less than 3% discontinuation due to cough in prior products.

• Device portability and rapid inhalation are designed for chronic use in elderly and compromised lung populations.