Safety and Efficacy of Venetoclax in Idiopathic Pulmonary Fibrosis

Number of participants with treatment-related adverse events as assessed by measuring liver function.,Number of participants with treatment-related adverse events as assessed by measuring blood counts.

Based on preclinical data, investigators hypothesize that apoptosis resistance in
 monocyte-derived macrophages (MDMs) have a decisive role in the development of idiopathic
 pulmonary fibrosis (IPF). Specifically, macrophages from subjects with IPF have increased
 expression of Bcl-2 in mitochondria. In preclinical models of IPF, a conditional deletion of
 Bcl-2 in MDMs reverses established fibrosis by inducing apoptosis. Additional evidence to
 suggest that Bcl-2 expression in MDM mitochondria is a therapeutic target for IPF as
 administration of the Bcl-2 inhibitor, ABT-199 (Venetoclax), showed marked efficacy in
 preclinical models of IPF by inducing apoptosis of MDMs and reversing established fibrosis.
 ABT-199 is an orally available mimetic of the BH3 domain of Bcl-2, which is the domain the
 anchors Bcl-2 in the mitochondria to inhibit apoptosis. ABT-199 has shown therapeutic
 efficacy and good safety and tolerability in patients with chronic lymphocytic leukemia.
 Investigators anticipate that treatment with ABT-199 could result in significant benefit for
 IPF patients that have a life expectancy of 3-5 years. As there is no curative therapy for
 IPF, this clinical trial has the potential to substantially alter treatment approaches in
 patients with IPF.