X-Rx Completes Early Studies on X-165 for Potential IPF Treatment, Supporting IND Application

Vijaya Iyer, PhD avatar

by Vijaya Iyer, PhD |

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Studies supporting an investigational new drug (IND) application for X-165, a potential candidate for the treatment of idiopathic pulmonary fibrosis (IPF) and other fibrotic disorders, have been completed, X-Rx recently announced.

According to the U.S. Food and Drug Administration, an IND application permits the manufacturer to transport the new drug across states for early-stage clinical testing without approved marketing rights. Preclinical data evaluating the product’s safety and toxicity are crucial in submitting a successful IND.

“With X-165, the most advanced asset in our internal portfolio, we have the exciting opportunity to bring forward an anti-fibrotic therapy that could add to current standard of care in a number of conditions, like IPF, where the unmet medical need is high and fibrosis is a key component of the pathophysiology,” Christelle Huguet, PhD, chief scientific officer of X-Rx, said in the press release.

X-165 is a small molecule that binds and inhibits the enzyme autotaxin. Autotaxin is responsible for the production of lysophosphatidic acid, a lipid (fat) molecule that promotes the synthesis of pro-inflammatory molecules.

High levels of autotaxin have been reported in IPF lungs. By binding to autotaxin, X-165 could block the production of lysophosphatidic acid, and potentially curb inflammation and tissue scarring, the characteristic symptoms of many fibrotic conditions including IPF.

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X-165 was discovered using the DNA-encoded drug discovery platform, DEX, developed by X-Chem Pharmaceuticals. This drug discovery platform includes a large library of molecules that have a DNA tag attached to them, and it enables highly selective identification of a cluster of lead molecules that bind to a target of interest, in this case autotaxin. Once bound, DNA sequencing methods are used to detect the small molecules.

Following the identification of the cluster, an optimization strategy is adopted to narrow down the leads, which can then be tested in several assays for their functionality.

Using this platform, X-165 was identified in an advanced screening trial containing more than 100 billion other molecules. It was narrowed down from among 150 other molecules with similar chemical structure (analogs), and its the activity was confirmed in conventional assays.

According to the company, X-165 strongly inhibits autotaxin, and showed encouraging results as an oral treatment in preclinical models of IPF compared with other analogous molecules.

Additional studies have also been completed on X-165 that will contribute to its IND application, the company said.

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