CAMBRIDGE, Mass., Nov. 11, 2019 /PRNewswire/ -- Indalo Therapeutics, a biopharmaceutical company discovering and developing integrin antagonists for patients suffering from serious fibrotic diseases such as idiopathic pulmonary fibrosis (IPF) and nonalcoholic steatohepatitis (NASH), for the first time presented clinical data for the company's lead antifibrotic drug candidate IDL-2965 at the Pulmonary Fibrosis Foundation (PFF) Summit on November 7. The data demonstrate excellent safety and tolerability at concentrations that are multiples of those anticipated to be necessary for efficacy, as well as strong oral pharmacokinetics supportive of once-daily oral dosing.
Indalo is studying IDL-2965 administered orally once daily in an adaptive multi-part Phase 1 clinical trial. The data presented at the PFF Summit relate to the recently completed first two parts of the protocol: single- and multiple-ascending dose (SAD and MAD) studies in normal healthy volunteers (NHVs). The SAD study explored a 120-fold dose range from 3 mg to 360 mg, while the MAD study explored doses from 15 mg to 135 mg administered once daily for 14 days. Dosing is ongoing in the third part of the protocol, a 28-day MAD study in IPF patients designed to measure safety, pharmacokinetics, and effects on a robust panel of target-engagement and disease biomarkers.
"Progressive fibrosing interstitial lung diseases (ILD) such as IPF remain a high unmet medical need associated with significant morbidity and mortality," commented Lead Author Dr. Toby Maher, the British Lung Foundation Chair in Respiratory Research and Professor of Interstitial Lung Disease at the National Heart and Lung Institute at Imperial College, London, UK. "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 ILD."
The proportion of subjects experiencing treatment-emergent adverse events was lower in those receiving IDL-2965 than placebo in both the single- and multiple-dose studies. There were no severe or serious adverse events, no treatment discontinuations, and no drug- or dose-related trends in adverse events, vital signs, laboratory tests, or electrocardiogram findings.
Plasma concentrations were robust and dose-proportional for oral doses up to 360 mg administered once, and at steady-state for oral doses up to 135 mg administered once daily for 14 days. The plasma half-life averaged approximately 20 hours, which is ideal for once-daily dosing.
"These data suggest that IDL-2965 can be safely dosed orally once daily to achieve plasma exposures well above those anticipated to be necessary for clinical efficacy," explained Indalo Chief Medical Officer Dr. Bill Bradford. "We are excited about our ongoing IPF program and plan to evaluate IDL-2965 in other serious fibrotic diseases."
IDL-2965 is an oral, selective antagonist of αvβ1, αvβ3, and αvβ6 that uniquely inhibits multiple fibrogenic processes, including the local activation of TGF-β (a central regulator of pathologic fibrosis) as well as the ability of stiff extracellular matrix to promote fibroblast migration and survival. This approach provides robust antifibrotic activity across a broad range of tissue types in preclinical models without having to rely on null-like suppression of a single target.
Indalo also presented non-clinical data supporting the potential for use of IDL-2965 in NASH at the American Association for the Study of Liver Diseases (AASLD) Liver Meeting in Boston, MA, which was held November 8 to 11, 2019.
About Indalo Therapeutics
Indalo Therapeutics is a biopharmaceutical company discovering and developing integrin antagonists for patients suffering from serious fibrotic diseases such as IPF and NASH. Indalo's approach is unique compared to other therapeutic options being explored as it directly targets multiple processes involved in pathologic fibrosis. Indalo's founders have investigated integrin antagonist biology and chemistry for decades, and its R&D leadership team was responsible for the development and approval of Esbriet® at InterMune. Atlas Venture and F-Prime Capital co-led the company's Series A financing in 2017. The company has also received funding from BioGenerator, MTC, iSelect Fund, and other investors. Indalo's corporate office is located in Cambridge, MA. For more information, please visit www.indalotherapeutics.com.
SOURCE Indalo Therapeutics