Agomab Reports Positive Phase 1 Results for AGMB-447 in Idiopathic Pulmonary Fibrosis

Phase 1 Study Shows Favorable Safety and Lung Exposure

Agomab Therapeutics NV has reported positive results from its Phase 1 clinical study of AGMB-447 in people with idiopathic pulmonary fibrosis (IPF).

AGMB-447 is an investigational inhaled medicine designed to treat IPF by blocking ALK5, also known as TGFβR1. The drug is designed to work mainly inside the lungs while keeping exposure in the rest of the body low.

The Phase 1 results showed a generally favorable safety and tolerability profile in IPF patients receiving the 4.5 mg twice-daily dose. The study also showed that AGMB-447 reached high levels in the lungs while maintaining low systemic exposure.

The findings have supported Agomab's plans to move AGMB-447 into a Phase 2 study called INSPIRIA.

What Is Idiopathic Pulmonary Fibrosis?

Idiopathic pulmonary fibrosis is a serious lung disease that causes scar-like tissue to build up inside the lungs.

As this tissue increases, the lungs become stiff. This makes it harder for patients to breathe and reduces the ability of the lungs to move oxygen into the blood.

IPF affects approximately 255,000 people across the United States, Japan and the largest European markets, including the EU4 and UK.

There are already three approved treatments for IPF. However, these medicines generally slow the progression of the disease rather than stopping it completely. Side effects can also make treatment difficult for some patients.

Without a lung transplant, median survival after an IPF diagnosis is only around three to five years.

What Is AGMB-447?

AGMB-447 is a small-molecule drug that is being developed as an inhaled treatment for IPF.

The medicine targets ALK5, which is also known as transforming growth factor beta receptor 1, or TGFβR1.

TGFβ is an important biological pathway involved in fibrosis, which is the process that causes excessive scar tissue to form in organs.

In IPF, uncontrolled fibrotic activity contributes to the gradual damage and stiffening of lung tissue.

Agomab is developing AGMB-447 to block this pathway directly in the lungs.

The Drug Is Designed to Stay Mainly in the Lungs

One of the main features of AGMB-447 is its lung-restricted design.

The medicine is delivered through inhalation using nebulization. This is intended to send the drug directly into the lungs rather than exposing the entire body to high drug levels.

AGMB-447 is also rapidly broken down in plasma into a main metabolite that is inactive inside cells. According to Agomab, this design is intended to limit clinically relevant systemic exposure.

The Phase 1 results provided clinical evidence supporting this approach.

Phase 1 Study Included Healthy Participants and IPF Patients

The Phase 1 program was divided into three parts.

Part A was a single ascending dose study in healthy participants. Doses ranged from 1 mg once daily to 20 mg once daily.

Part B was a multiple ascending dose study in healthy participants. Doses ranged from 1 mg once daily to 6 mg twice daily.

Part C studied multiple doses in patients with IPF. Doses ranged from 4.5 mg twice daily to 6 mg twice daily.

AGMB-447 was given through nebulization. Participants in the single-dose portion received one dose, while Part B involved seven days of treatment and Part C involved 14 days of treatment.

A total of 10 patients with IPF were included in Part C.

Safety Results Were Generally Favorable

The safety findings in IPF patients were generally consistent with the earlier results seen in healthy participants.

At the 4.5 mg twice-daily dose, AGMB-447 showed a generally favorable safety and tolerability profile.

A higher number of adverse events was reported at the 6 mg twice-daily dose. However, Agomab said that no new specific safety signals were identified.

Importantly, no systemic safety signals were detected at any of the doses tested.

The most frequently reported adverse events were cough and bronchospasm.

The cough episodes were generally short and mostly occurred during the inhalation period. The company also reported that there was no increase in the severity of disease-related cough during the 14-day treatment period.

AGMB-447 Reached High Levels in the Lungs

The Phase 1 study also provided important information about how AGMB-447 behaves in the body.

Researchers found low systemic exposure but high pulmonary exposure in IPF patients. This supports the idea that the drug can reach the lungs while limiting exposure elsewhere in the body.

At the 4.5 mg twice-daily dose, average AGMB-447 levels in bronchoalveolar lavage fluid remained above the IC90 level for at least six hours after inhalation.

The levels also remained above the IC50 level for 24 hours.

These findings were consistent with the pharmacokinetic profile previously observed in healthy participants.

In simple terms, the drug appeared to stay active in the lungs for a meaningful period after inhalation while maintaining relatively low exposure throughout the rest of the body.

The Study Showed Strong Target Engagement

The study also looked at whether AGMB-447 was actually affecting its intended biological target.

Researchers measured pSMAD3 levels in cells collected from bronchoalveolar lavage fluid. pSMAD3 is a marker used to assess activity in the TGFβ signaling pathway.

At the 4.5 mg twice-daily dose, AGMB-447 produced more than a 50% reduction in pSMAD3 in these cells.

This suggests that the drug was successfully engaging the TGFβ/ALK5 pathway in the lungs of IPF patients.

For Agomab, this provides proof-of-mechanism evidence that the drug is producing the biological effect it was designed to produce.

Agomab Plans Phase 2 INSPIRIA Study

Based on the Phase 1 results, Agomab is preparing to begin its Phase 2 INSPIRIA study.

INSPIRIA will be a 24-week, randomized, double-blind and placebo-controlled study involving approximately 120 patients with confirmed IPF.

Patients will be randomized in a 2:1 ratio to receive either AGMB-447 or placebo.

The planned AGMB-447 dose is 4 mg twice daily, administered through inhalation on top of standard-of-care treatment.

The study will evaluate the safety, pharmacokinetics and efficacy of AGMB-447 in people with IPF.

The main efficacy endpoint will be the change from baseline in forced vital capacity at Week 24.

Forced vital capacity, or FVC, measures how much air a person can forcefully breathe out after taking a deep breath. It is commonly used to monitor lung function in IPF.

INSPIRIA Study Expected to Start in the Second Half of 2026

Agomab has submitted the clinical trial application for INSPIRIA.

The company expects the study to begin during the second half of 2026.

The trial is planned to take place across a large network of European clinical sites.

The Phase 2 study will give researchers a better understanding of whether the biological activity seen in Phase 1 can translate into meaningful improvements in lung function and other measures of IPF.

Experts See Potential in Local ALK5 Inhibition

Toby Maher, M.D., PhD, Professor of Clinical Medicine at the Keck School of Medicine of USC, said the TGFβ pathway has long been recognized as an important driver of fibrosis in IPF.

He said targeting this pathway through ALK5 inhibition with AGMB-447 could be a promising approach.

The planned twice-daily dosing schedule could also allow AGMB-447 to be studied as a standalone treatment or potentially alongside systemic standard-of-care therapies.

The INSPIRIA study is intended to explore this potential further in people living with IPF.

Agomab Says the Phase 1 Results Support Further Development

Philippe Wiesel, Chief Medical Officer at Agomab, said the company was pleased with the Phase 1 results in IPF patients.

According to Agomab, the study showed a generally favorable safety, tolerability and pharmacokinetic profile. The company also said the results provided proof-of-mechanism for TGFβ/ALK5 inhibition in the lungs.

Agomab believes that blocking the TGFβ/ALK5 pathway locally in the lung could potentially provide an anti-fibrotic treatment option while limiting systemic exposure.

The company plans to present more detailed Phase 1 results at a future scientific conference.

AGMB-447 Is Still an Investigational Medicine

AGMB-447 has not been approved by any regulatory authority.

Its safety and effectiveness have not yet been established.

The upcoming Phase 2 INSPIRIA study will therefore be important in determining whether the treatment can demonstrate clinical benefits in a larger group of IPF patients.

Agomab's Focus on Fibro-Inflammatory Diseases

Agomab is a clinical-stage biopharmaceutical company developing treatments for fibro-inflammatory diseases with high unmet medical needs.

The company's drug candidates are designed to target established biological pathways while using organ-restricted approaches where possible.

The goal is to increase treatment activity in the affected organ while reducing safety concerns that can come from exposing the rest of the body to higher drug levels.

With AGMB-447, Agomab is applying this approach to IPF by delivering an ALK5 inhibitor directly to the lungs.

The company is now preparing for the next stage of development, with the INSPIRIA Phase 2 study expected to begin in the second half of 2026.