Agomab reports positive Phase 1 data for inhaled IPF drug AGMB-447

Agomab Therapeutics has announced positive topline results from the Phase 1 study of AGMB-447, its inhaled small-molecule inhibitor of ALK5, in patients with idiopathic pulmonary fibrosis (IPF). The Antwerp-based company said the data support progression into a randomised Phase 2 study, known as INSPIRIA, for which a Clinical Trial Application has already been submitted to European regulators.

AGMB-447 works by blocking the TGFbeta/ALK5 pathway locally in the lung. The drug is designed to achieve high pulmonary exposure while limiting systemic absorption, a profile intended to reduce the off-target safety liabilities that have historically constrained systemic TGFbeta inhibitors. The Phase 1 programme enrolled a total of 10 IPF patients in its third part, receiving doses of either 4.5 mg or 6 mg twice daily via nebulisation over 14 days.

Phase 1 results

At the 4.5 mg twice-daily dose, AGMB-447 was reported to have a generally favourable safety and tolerability profile, with no systemic safety signals identified at any dose. A higher incidence of adverse events was noted at 6 mg twice daily, though no new specific signals emerged. The most commonly reported events were cough and bronchospasm, with cough episodes described as short and largely confined to the inhalation period.

Pharmacokinetic data confirmed the lung-restriction thesis. Bronchoalveolar lavage fluid concentrations at 4.5 mg twice daily exceeded the IC90 threshold for at least six hours post-inhalation and remained above IC50 for a full 24 hours. On the pharmacodynamic side, pSMAD3 reduction in BAL cells exceeded 50% at the same dose, indicating robust target engagement of the ALK5 pathway in diseased lung tissue.

Philippe Wiesel, Chief Medical Officer at Agomab, said the data provided "proof-of-mechanism of TGFbeta/ALK5 inhibition in the lungs of IPF patients" and confirmed the programme's readiness for Phase 2.

INSPIRIA Phase 2 design and market context

INSPIRIA is designed as a 24-week, randomised, double-blind, placebo-controlled study in approximately 120 patients with confirmed IPF. Participants will be assigned in a 2:1 ratio to receive AGMB-447 4 mg twice daily or placebo, on top of standard-of-care therapy. The primary endpoint is change from baseline in forced vital capacity at week 24. Agomab said it expects to initiate the study before the end of 2026 across a European site network.

IPF affects roughly 255,000 patients across the US, Japan, and the four largest European markets plus the UK. Three approved therapies exist, but none halts disease progression outright; median survival following diagnosis remains three to five years. That persistent unmet need has attracted a wave of development activity focused on novel mechanisms, and the TGFbeta pathway has long been considered a compelling but difficult target because of the broad role the signalling cascade plays in healthy tissue.

Agomab's inhaled, organ-restricted approach is designed to sidestep systemic TGFbeta inhibition toxicity, a strategy that differentiates AGMB-447 from earlier-generation small molecules that failed due to cardiovascular and other off-target effects. Several other groups are pursuing inhaled or locally delivered anti-fibrotic strategies, making the forced vital capacity readout from INSPIRIA a closely watched data point for the field. Full Phase 1 results are expected to be presented at a future scientific conference.