Agomab's Inhaled ALK5 Inhibitor AGMB-447 Shows Target Engagement in IPF Phase 1, Phase 2 INSPIRIA Set for Late 2026
核心洞察
Agomab (搜索) reported positive Phase 1 results for inhaled AGMB-447 in 10 patients with idiopathic pulmonary fibrosis (搜索), showing proof of TGF-beta (搜索)/ALK5 (搜索) inhibition in the lungs.
At 4.5 mg twice daily for 14 days, lung concentrations remained high enough to inhibit ALK5 (搜索) while systemic exposure stayed low, and pSMAD3 fell by more than 50%.
The 4.5 mg dose was generally well tolerated, with cough and bronchospasm the most common adverse events and more events reported at 6 mg.
Agomab (搜索) has reported positive Phase 1 results for AGMB-447, an inhaled, lung-restricted small molecule inhibitor of ALK5 (搜索) (TGF-betaR1), in patients with idiopathic pulmonary fibrosis (搜索) (IPF), and disclosed the design of its planned Phase 2 INSPIRIA study.
The Phase 1 trial tested AGMB-447 in 10 people with IPF who received either 4.5 mg or 6 mg twice daily for 14 days. At the 4.5 mg dose, lung concentrations remained high enough to inhibit ALK5 (搜索) while systemic exposure remained low. Levels of pSMAD3, a downstream marker of the TGF-beta (搜索) pathway, fell by more than 50%, indicating that the pathway was being inhibited in the lungs.
"We are very pleased with the Phase 1 results of AGMB-447 in patients with IPF announced today. In line with the positive interim data in healthy participants announced earlier this year, the data indicated a generally favorable safety, tolerability and PK profile of AGMB-447 and provided proof-of-mechanism of TGF-beta (搜索)/ALK5 (搜索) inhibition in the lungs of IPF patients," said Philippe Wiesel, Chief Medical Officer at Agomab (搜索).
Safety and tolerability
The 4.5 mg dose was generally well tolerated. Agomab (搜索) reported more adverse events at 6 mg, with cough and bronchospasm the most common, although the company reported no new specific or systemic safety signals.
The design of AGMB-447 is intended to address the central obstacle to targeting this pathway. TGF-beta (搜索) signaling is an important driver of fibrosis and an attractive target in IPF, but inhibiting ALK5 (搜索), the receptor that transmits TGF-beta signals into cells, throughout the body has been held back by safety concerns. AGMB-447 is administered by inhalation directly into the lung, where it blocks the TGF-beta signals that activate fibroblasts and drive the buildup of scar tissue. Drug that enters the bloodstream is rapidly hydrolyzed in plasma into one main metabolite that is inactive in cells, limiting systemic exposure.
"We believe that by blocking the TGF-beta (搜索)/ALK5 (搜索) pathway locally in the lung, AGMB-447 has the potential to offer a potent anti-fibrotic therapy to IPF patients. The extensive data collected in our broad Phase 1 program supports the initiation of our Phase 2 INSPIRIA study later this year," Wiesel said.
INSPIRIA Phase 2 design
INSPIRIA is a 24-week, randomized, double-blind, placebo-controlled Phase 2 study in approximately 120 patients with confirmed IPF. Patients will be randomized 2:1 to receive AGMB-447 4 mg twice daily or placebo, administered by inhalation on top of standard of care. The study is designed to evaluate safety, pharmacokinetics and efficacy. The primary endpoint is change from baseline in forced vital capacity at Week 24.
The clinical trial application for INSPIRIA has been submitted, and the study is anticipated to begin in the second half of 2026 across a large European site network. Agomab (搜索) intends to present detailed Phase 1 results at a future scientific conference.
"We have long known that the TGF-beta (搜索) pathway is a central driver of fibrosis in IPF. Targeting this key pathway through ALK5 (搜索) inhibition with AGMB-447 is a promising approach. With a convenient twice-daily dosing schedule, AGMB-447 could represent an attractive option for monotherapy or combination therapy with systemic standard of care therapies. The INSPIRIA study is designed to further explore the therapeutic potential of this novel inhaled approach in people living with IPF," said Toby Maher, M.D., PhD, Professor of Clinical Medicine at Keck School of Medicine of USC.
Treatment landscape and remaining questions
IPF affects approximately 255,000 patients in the U.S., Japan and the largest European markets (EU4+UK). The disease is characterized by unregulated production of fibrotic, scar-like tissue that builds up in the scaffolding of the lungs, making the lung stiff, hampering the patient's ability to breathe and reducing the absorption of inhaled oxygen in the blood. Without a lung transplant, median survival following diagnosis is only 3 to 5 years. Three approved therapies are commercially available, but they do not halt disease progression, only slow it, and their side effects reduce tolerability and lead to treatment discontinuations.
The treatment landscape expanded in 2025 when Boehringer Ingelheim's nerandomilast became the first new U.S.-approved therapy for the disease in more than a decade, joining the antifibrotics nintedanib and pirfenidone. AGMB-447 would bring a different approach and is being developed for use on top of existing treatment.
The Phase 1 data do not yet show whether AGMB-447 can slow IPF. Only 10 patients received the drug, for 14 days, and the study assessed safety, drug exposure and target engagement. Clinical efficacy is the next step. AGMB-447 is an investigational drug and has not been approved by any regulatory authority; its efficacy and safety have not been established.