First IPF Patient Dosed in Phase 1 Trial of Potential Oral Anti-fibrotic Therapy, Indalo Announces

Indalo Therapeutics announced that dosing has begun in the first patient enrolled in its Phase 1 trial assessing the safety, tolerability, and properties of IDL-2965, the company’s lead candidate to treat fibrotic diseases including idiopathic pulmonary fibrosis (IPF).

IDL-2965 is an oral, selective antagonist of three types of integrins — αvβ1, αvβ3, and αvβ6 — which are proteins that form the extracellular matrix (the network that surrounds and supports cells).

By inhibiting these integrins, IDL-2965 works to block a pro-fibrotic signaling cascade triggered by the activation of transforming growth factor beta (TGF-β) and, at the same time, prevent the matrix from becoming stiff, which is also linked to tissue fibrosis (scarring).

This three-part Phase 1 trial (NCT03949530) is investigating the safety, tolerability, and pharmacokinetics (drug absorption, distribution, and elimination) of IDL-2965 given once a day, first to healthy volunteers and later to IPF patients.

The company recently completed the study’s first two parts, which involved testing the effects of single and multiple-ascending doses of IDL-2965 in healthy volunteers. Here, a 120-fold dose range of the compound was tested in 80 people, and IDL-2965 showed a favorable safety and pharmacokinetic profile, the company reported.

Indalo has now started administering IDL-2965 to IPF patients participating in the trial’s third phase. Patients will receive multiple-ascending doses of the oral therapy over 28 days to determine its safety, pharmacokinetics, and effects on biomarkers of fibrosis.

“The safety, tolerability, and pharmacokinetics of IDL-2965 in NHVs [normal healthy volunteers] to date are very encouraging, clearly supporting once-daily oral dosing and advancement into the IPF patient MAD [multiple-ascending doses] part of the trial,” Toby Maher, coordinating investigator, chair in Respiratory Research for the British Lung Foundation and a professor at the National Heart and Lung Institute at the Imperial College of London, said in a press release.

“IDL-2965 has potential in multiple fibrotic diseases including those involving the lung, liver, and kidney,” Bill Bradford, chief medical officer of Indalo, added. “IPF is an attractive first indication for IDL-2965 given the high unmet medical need as well as the demonstrated responsiveness of target-engagement and disease biomarkers to pharmacologic intervention.”

The study may still be enrolling adult patients at its one site in Leeds; information is available here.

Indalo is planning to present data from the trial’s first two parts at the Pulmonary Fibrosis Foundation (PFF) Summit in San Antonio, Texas, set for Nov. 7–9.