Cudetaxestat for IPF Found Safe in Phase 1 Trial of Healthy Volunteers

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by Vanda Pinto, PhD |

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Cudetaxestat (BLD-0409), an investigational therapy for idiopathic pulmonary fibrosis (IPF), showed favorable safety and tolerability in a Phase 1 trial of healthy volunteers.

Developed by Blade Therapeutics, cudetaxestat is designed to block the activity of an enzyme called autotaxin that produces a pro-scarring (fibrotic) signaling molecule. This enzyme commonly is overactive in people with IPF and other fibrotic disorders.

Blocking autotaxin activity and the release of pro-fibrotic signals is expected to reduce tissue scarring in these patients.

The therapy’s pharmacological properties and safety were evaluated in the Phase 1 trial (NCT04814498), sponsored by Blade, which involved 16 healthy adults. Researchers also tested the effect of cudetaxestat on the pharmacokinetics, or movement throughout the body, of a combination of different compounds, called probe substrates, used to assess various enzymes known as CYP450.

There are more than 50 CYP450 enzymes, which are important for processing certain medications, and their activities can be tested with these probe substrates.

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In this trial, volunteers received a cocktail of probe substrates for the CYP450 enzymes CYP1A2, CYP2C, CYP2C19, CYP2D6, CYP3A4, and CYP2B6, as well as cudetaxestat, via an into-the-abdomen (intraperitoneal) injection, given after an overnight fast of 10 hours.

According to Blade, blood levels of the substrates for CYP3A4, CYP2B6, CYP1A2, and CYP2C remained unaltered. CYP2D6 was inhibited, weakly, while CYP2C19 was activated.

Cudetaxestat was found to have a positive safety and tolerability profile. No severe adverse events nor drop-outs caused by such side effects were reported.

“We are pleased with these clinical data that add to our expanding knowledge base about the supportive safety and tolerability profiles of cudetaxestat,” Wendye Robbins, MD, president and CEO of Blade, said in a press release.

“This study continues the momentum of our development program and supports advancing cudetaxestat in the anticipated patient populations,” Robbins said.

Robbins said Blade “remains on track” with its plans to launch a Phase 2 study of cudetaxestat in people with IPF in the first half of 2022.

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Blade recently completed another Phase 1 trial (NCT04814472) testing the investigational therapy in healthy volunteers. That trial revealed that the original oral solution of cudetaxestat had similar pharmacological properties and an identical safety profile to those of a new tablet formulation.

Another Phase 1 trial (NCT04939467), which is recruiting participants, also has been launched to determine how cudetaxestat interacts with two approved IPF treatments, Ofev (nintedanib) and Esbriet (pirfenidone).

Both Ofev, by Boehringer Ingelheim, and Esbriet, now being investigated and marketed by Genentech, are approved for use in the U.S., Europe, and other countries.

Additionally, the company announced that cudetaxestat had achieved other milestones, including orphan drug designation for the treatment of systemic sclerosis, a rare condition characterized by scarring of the skin, joints, and internal organs. Orphan drug status is granted by the U.S. Food and Drug Administration to investigational treatments for conditions affecting less than 200,000 people in the U.S. Benefits of the status include tax credits, FDA funding toward clinical trial costs, and seven years of marketing exclusivity, if the therapy is approved.