Indalo Therapeutics’ lead investigational anti-fibrotic candidate, IDL-2965, is safe and shows favorable pharmacokinetics (absorption, distribution, and elimination in the body) in healthy people, according to interim results of a Phase 1/2a clinical trial.
The results were presented at the Pulmonary Fibrosis Foundation (PFF) Summit, held Nov. 7–9 in San Antonio, Texas.
IDL-2965 is an orally-taken small molecule that selectively targets three integrins — αvβ1, αvβ3, and αvβ6 — which are cell-membrane receptors that bind to and interact with the extracellular matrix (the network that surrounds and supports cells).
By blocking these integrins, IDL-2965 suppresses the activation of transforming growth factor beta (TGF-β), a protein involved in tissue scarring (fibrosis), and prevents stiffening of the extracellular matrix, which also is linked with fibrosis.
Previous studies in animal models showed that the therapy had anti-fibrotic effects across several vital organs, including the liver, lung, and kidney, at low doses.
The three-part Phase 1/2a clinical study (NCT03949530) is now evaluating the safety, tolerability, and pharmacokinetics of different oral doses of IDL-2965, compared with a placebo, first in healthy volunteers and later in people with idiopathic pulmonary fibrosis (IPF).
At the meeting, the company presented data from the first two recently-completed parts of the study, which involved the investigation of the effects of single- and multiple-ascending doses of IDL-2965 in 80 healthy volunteers.
In the single-dose study researchers explored a 120-fold dose range from 3 mg to 360 mg of IDL-2965 given once, while the multiple-dose study analyzed doses from 15 mg to 135 mg given daily for 14 days.
Results showed that IDL-2965 levels in the blood were robust and proportional to the given dose, and that daily dosing resulted in constant and potentially clinically meaningful levels in the blood. These levels were above those anticipated to be necessary for effectiveness, according to the company.
IDL-2965 blood levels were reduced by half in approximately 20 hours, suggesting that its action duration is ideal for once-daily dosing.
“These data suggest that IDL-2965 can be safely dosed orally once daily to achieve [blood levels] well above those anticipated to be necessary for clinical efficacy,” Bill Bradford, MD, Indalo’s chief medical officer, said in a press release.
Safety data demonstrated that none of the tested doses led to severe or serious adverse events (side effects) or treatment discontinuations, and there were no treatment- or dose-related trends in adverse events. Also, in both single- and multiple-dose studies, adverse events occurred in a smaller proportion of participants receiving IDL-2965, compared with those on placebo.
Overall, the findings highlighted that IDL-2965 has a strong safety and tolerability profile — even at higher doses— as well as favorable pharmacokinetics that support once-daily oral dosing.
“The unique and compelling mechanism of action of IDL-2965 coupled with these favorable data support the ongoing IPF Proof-of-Biology study, and additional studies in [other interstitial lung diseases],” said Toby Maher, MD, the study’s lead author. Maher is chairman of respiratory research at the British Lung Foundation, and professor at the National Heart and Lung Institute at Imperial College, London, England.
The third part of the study, which is already underway, is assessing the safety, pharmacokinetics, and effects on IPF biomarkers of multiple-ascending doses of IDL-2965, given over 28 days, in IPF adult patients.
“We are excited about our ongoing IPF program and plan to evaluate IDL-2965 in other serious fibrotic diseases,” including diseases such as nonalcoholic steatohepatitis (NASH), Bradford said.