GB0139, Galecto’s lead compound to treat various fibrotic diseases of the lungs, has shown strong anti-fibrotic activity in a mouse model of idiopathic pulmonary fibrosis (IPF) and in IPF patients in a completed Phase 2a trial.
A randomized, double-blind and placebo controlled Phase 2b trial (NCT03832946) of this inhalation treatment is now underway at sites across the U.S., Europe, Canada, and Israel, and may be enrolling eligible IPF patients.
These preclinical and clinical findings were announced by the company in an abstract, “Translational pharmacology of TD139, an inhaled small molecule galectin‐3 (Gal‐3) inhibitor for the treatment of idiopathic pulmonary fibrosis (IPF),” submitted for a poster presentation at the Experimental Biology 2020 conference. The meeting was canceled due to COVID-19.
GB0139, formerly known as TD139, is an inhaled, small molecule inhibitor of galectin-3, a protein produced in high levels in the lungs of IPF patients and known to promote tissue scarring (fibrosis) and inflammation. By blocking the activity of galectin-3, GB0139 is expected to lessen lung fibrosis.
Although being developed to treat most lung fibrotic diseases, Galecto is focusing its development on IPF, which is estimated to affect around 100,000 people in the U.S. alone.
New findings presented in the poster included preclinical data from in vivo studies assessing the effectiveness of GB0139 at reducing the levels of galectin-3 in a mouse model of IPF, as well as data from in vitro or lab dish studies evaluating GB0139’s target engagement. Of note, target engagement is a therapy’s ability to interact with its intended therapeutic target, in this case with galectin-3.
In vitro studies confirmed GB0139’s ability to recognize and bind to galectin-3 with high affinity. The in vivo studies in a mouse model of IPF showed that GB0139 has strong anti-fibrotic activity, effectively lower galectin-3 levels in the animals’ lungs.
In addition to this preclinical data, the company announced findings from a multicenter, double-blind and placebo-controlled Phase 2a trial (NCT02257177) that investigated the safety, tolerability, and pharmacological properties of GB0139 in 24 IPF patients.
In the trial, which ended in December 2016, patients were randomly assigned to one of three doses of GB0139 — 0.3 mg, 3 mg, or 10 mg — or t0 a placebo once-a-day for 14 days.
All underwent bronchoalveolar lavage (BAL) before and after completing the 14-day treatment period. (BAL is a procedure used to examine inflammation and other processes taking place in the lungs; a fluid is squirted via a tube or bronchoscope into a small portion of the airways, and then collected to be analyzed.)
Patient BAL samples were used to isolate macrophages, a type of immune cells known to contribute to lung inflammation and scarring in IPF. Levels of GB0139 were measured in BAL samples, lung macrophages, and plasma samples.
Treatment was well-tolerated at all doses tested, with drug concentrations in lung macrophages reaching levels that were more than 567‐fold higher than those in blood plasma, the study’s researchers reported.
Treatment also led to dose-dependent drops in the levels of galectin-3 found in lung macrophages, ranging from a mean reduction of 52.52% in patients given the trial’s medium dose (3 mg GB0139), to a mean reduction of 78.60% in those treated at the highest dose (10 mg), compared with the placebo group.
These reductions in galectin-3 levels in lung macrophages were also associated with lower plasma levels of IPF biomarkers, including PAI-1, YKL‐40, and PDGF-BB.
Based on the results, the researchers concluded that “TD139 is safe and well tolerated in man and demonstrates low systemic exposure coupled with high lung concentrations resulting in suppression of Gal-3 on BAL macrophages and decreased plasma biomarkers associated with IPF progression.”
The ongoing Phase 2b trial is evaluating the safety and efficacy of inhaled GB0139 in up to 450 IPF patients, ages 40 and older, including those on stable standard of care. Treatment will be given at one of two doses, 3 mg once daily or 10 mg once daily, and compared with placebo over one year. Its main goal is changes from study start (baseline) at week 52 in forced vital capacity (FVC), a measure of the total amount of air expelled in one forced breath.
“These data are a further reinforcement of our belief in the potential success of GB0139 based on its mechanism, the targeting of the key regulator galectin-3, in anti-fibrotic diseases where there is a significant unmet medical need,” Hans Schambye, CEO of Galecto, said in a press release.
“We are looking forward to results from our ongoing Phase 2b trial in 450 IPF patients in 2022, in which the aim is to show clinically meaningful changes in lung function,” Schambye added.
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