FDA Clears Way for First Trials of IPF Treatment Candidate X-165

The U.S. Food and Drug Administration (FDA) has cleared the way for X-Rx’s idiopathic pulmonary fibrosis (IPF) therapy candidate X-165 to move into the first clinical tests. 

The FDA approved X-Rx’s Investigational New Drug (IND) application for the candidate, letting the company plan to start a Phase 1 trial soon.

X-165 is a highly potent small molecule inhibitor of the enzyme autotaxin. Autotaxin is responsible for the production of lysophosphatidic acid, a fat (lipid) molecule that triggers the release of pro-inflammatory molecules.

Increased levels of autotaxin and lysophosphatidic acid have been reported in lung cells and fluids (referred to as bronchoalveolar lavage, BAL) of IPF patients and animal models of pulmonary fibrosis. By inhibiting the activity of autotaxin, X-165 is expected to block the production of lysophosphatidic acid and restrict inflammation and tissue scarring — two hallmarks of many fibrotic conditions, including IPF.

X-165 was discovered through an initial screen of over 100 billion molecules using X-Chem’s DEX drug discovery engine. DEX is a DNA-encoded drug discovery platform based on a large library of molecules attached to unique and short DNA sequences, or DNA tags. It enables highly selective identification and narrowing down of lead molecules that bind to a target of interest, in this case autotaxin.

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According to X-Rx, X-165 has shown encouraging efficacy and safety results in preclinical studies. In animal models of pulmonary fibrosis, the therapy inhibited lung scarring when delivered orally, while presenting a favorable safety profile in toxicology studies. 

These results supported the product’s IND application. An IND application gives the drug’s manufacturer permission to ship the therapy across the U.S. for early-stage clinical testing before it has marketing approval.

The trial X-Rx is planning will be a randomized, placebo-controlled, single- and multiple-dose escalation study to assess the safety, tolerability, and pharmacokinetics (the body’s uptake, distribution, metabolism and elimination of the therapy) of oral X-165 in healthy volunteers.

“The upcoming clinical trial marks a major milestone for X-Rx, as X-165 becomes the second to reach the clinic, and the first candidate discovered using X-Chem’s DEX DNA encoded library technology,” Christelle Huguet, PhD, X-Rx’s chief scientific officer, said in a company press release.

“It is exciting to bring forward an anti-fibrotic therapy which 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,” Huguet said.