Blade Therapeutics will expand its pipeline in the field of fibrotic diseases with the acquisition of Atxco and its lead candidate PAT-409, which is ready to enter Phase 1 clinical studies.
PAT-409 was engineered to specifically inhibit the autotaxin enzyme involved in the production of a fatty molecule called lysophosphatidic acid, which plays a role in inflammation and scarring (fibrosis) in the lung, kidney, and liver.
Evidence shows that autotaxin levels are greatly increased in the lungs of people with idiopathic pulmonary fibrosis (IPF). Therefore, by inhibiting this enzyme, PAT-409 has the potential to reduce inflammation and fibrosis, and thereby halt the progression of IPF.
“As Atxco evaluated opportunities for PAT-409, it became clear that Blade’s commitment to patients with fibrosis and best-in-class team provide an excellent vehicle for its future development,” Robert Williamson, president and CEO of Atxco, said in a news release.
The investigational compound has shown an ability to reduce tissue damage and fibrosis in multiple preclinical models, and across various tissues and organs. It has also been shown to induce significant changes in gene activity, compared with other clinical autotaxin inhibitors — this difference is believed to support a greater therapeutic effect for PAT-409.
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“With the addition of this IND [investigational new drug] enabled program to our pipeline, we advance our agenda to bring innovative treatments to patients with fibrotic disorders,” said Wendye Robbins, MD, president and CEO of Blade.
“Autotaxin inhibition offers a distinct but complementary anti-fibrotic mechanism to our lead program, BLD-2660, a calpain inhibitor,” Robbins added. “We believe our two anti-fibrosis programs will each succeed as standalone therapies and potentially serve as elements for combination treatment.”
Blade Therapeutics is currently exploring the safety and impact of its small molecule calpain inhibitor BLD-2660. Calpain belongs to a family of enzymes called proteases that play an important role in protein degradation, and that can also regulate inflammation, cell migration, and other cellular and molecular processes.
Preclinical studies demonstrated that BLD-2660 has a strong anti-fibrotic activity in multiple animal models of pulmonary, skin, and liver fibrosis.
BLD-2660 is being evaluated in a Phase 1 dose-escalating trial in healthy volunteers in Australia. Its results are expected to support an investigational new drug application to be submitted to the U.S. Food and Drug Administration.