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ENV-101: Changing the Trajectory of Fibrotic Lung Diseases

Endeavor’s lead investigational candidate, ENV-101, has the potential to improve lung function and reverse the fibrotic process in the lungs of individuals with idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF).

Idiopathic Pulmonary Fibrosis: Wound Healing Gone Wrong

In healthy lungs, any damage to alveoli, the tiny, critical air sacs that provide exchange of oxygen with the blood, triggers a normal and temporary wound-healing response in the body.

A cellular signaling pathway known as Hedgehog (Hh) plays a crucial role in this wound-healing process by driving the transition of fibroblasts to myofibroblasts that repair cellular damage. In patients with IPF, repeated environmental injury to cells in the lungs leads to abnormal activation of the Hh pathway and excessive buildup of fibrotic scarring in the lungs.

What is a Hedgehog gene?

In 1980, Christine Nusslein-Volhard and Eric Wiechaus identified a gene that plays a critical role in embryonic developments in fruit flies. Flies with a non-functioning version of this gene had several significant abnormalities, including external bristles that clump together rather than being evenly spaced, making them look something like a hedgehog. Thirteen years later, researchers in the Tabin Lab identified the mammalian version of hedgehog. A postdoctoral fellow in the lab, Robert Riddle, named this gene Sonic Hedgehog after the character in a comic book that his daughter brought home.

Endeavor BioMedicines’ investigational medicine ENV-101 is an Hh signaling pathway inhibitor. By binding to and inhibiting a key receptor in the Hh pathway, ENV-101 stops the abnormal accumulation of the myofibroblasts that cause fibrosis. This may resolve the excessive wound-healing process seen in IPF and PPF, creating the potential to reverse fibrosis and improve lung volume and function.

Data from a Phase 2a, randomized, double-blind, placebo-controlled clinical trial that evaluated safety and efficacy of ENV-101 vs. placebo in 41 patients with confirmed IPF who were treated for three months demonstrate the compound improved lung function and reversed key measures of lung fibrosis in patients with idiopathic pulmonary fibrosis. Further clinical investigation is forthcoming in a Phase 2 study in patients with IPF or PPF.

“By focusing on the Hedgehog pathway, we seek to disrupt a primary disease mechanism and create the potential to reverse lung fibrosis in patients.”

Miguel de los Rios, PhD
Co-Founder and Chief Scientific Officer