TD139 is an inhibitor of galectin-3, a protein known to play a key role in fibrosis in several organs, including the lungs. Previous studies have shown that inhibiting galectin-3 reduced or even prevented fibrosis in animal models.
The trial (NCT02257177) was divided into two parts. Phase 1b was a randomized, double-blind, single-center, placebo-controlled, single ascending dose study designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of TD139 in 36 healthy men. Pharmacokinetics refers to how a drug behaves in the body, and pharmacodynamics to how the body reacts to a drug.
Phase 2a was a randomized, double-blind, multi-center, placebo-controlled, multiple dose expansion trial. It was designed to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of TD139 in up to 24 IPF patients. Some were men and some women with no childbearing potential.
TD139 was found to be well tolerated in all patients.
The trial showed that the larger the dose, the more effect it had on a patient — a characteristic known as proportional systemic exposure. The evaluation team also said that TD139 had a favorable half-life. That is the amount of time required for the concentration of a drug in the body to be halved.
Absorption of the drug in alveolar macrophages, the cell the therapy targets, was also favorable, mirroring systemic exposure, Galecto said.
“TD139 has shown ground-breaking results in this proof of concept study in individuals with IPF raising the prospect that this compound could represent an important future therapeutic option for this devastating disease,” Toby Maher, of the Royal Brompton Hospital and Imperial College London, said in a press release. He was the lead trial investigator.
“Galecto’s IPF trial has resulted in a paradigm shift for studying disease modifying agents for lung disease,” said Nikhil Hirani of the Edinburgh Medical School, who was the trial’s principal investigator.
“By performing bronchoscopies before and after the treatment period, we have been able to detect biomarker changes in plasma and alveolar cells whilst also precisely quantifying the amount of TD139 that has reached the target cell. This has to my knowledge never been done before – neither with a potential IPF treatment nor with an inhaled drug of any kind,” Hirani added.
Galecto will present detailed results of the trial at the next meeting of the American Thoracic Society (ATS 2017) in Washington in May.