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Antibody-based Therapy Prevents Granuloma Formation in Cell Model


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XTMAB-16, Xentria‘s investigational antibody-based therapy for treating sarcoidosis, was able to reduce the formation of granulomas — the abnormal clumps of immune cells that mark the disease — in a patient-derived cell model of granuloma, the company reported.

The data were presented in a poster titled “XTMAB-16 Attenuates Granuloma Formation in a Human In Vitro Sarcoidosis Model” at the American Thoracic Society 2022 International Conference in San Francisco on May 17.

“These new data are a promising first step in the continued evaluation of XTMAB-16 as a potential therapy for patients with sarcoidosis,” Thomas Shea, president of Xentria, said in a press release. “The release of this new data reinforces our commitment to the sarcoidosis rare disease community and our mission to develop new breakthrough treatments.”

Granuloma buildup impairs the normal function of various tissues and can affect the function of nearly all of the body’s organs, most commonly the lungs.

By suppressing activity of TNF-alpha, a pro-inflammatory molecule that contributes to swelling, inflammation, and granuloma formation, XTMAB-16 is expected to ease symptoms.

Although no TNF-alpha inhibitors are currently approved in the U.S. to treat sarcoidosis, a previous study showed about 10% of patients are being treated with such therapies off-label. In 2020, the U.S. Food and Drug Administration granted XTMAB-16 orphan drug designation for treating sarcoidosis, which is intended to accelerate the therapy’s development.

Researchers from Xentria and The Ohio State University evaluated the effects of XTMAB-16 on granuloma formation in a cell culture granuloma model. To generate it, cells were obtained from 10 sarcoidosis patients with lung and/or lymph node involvement and incubated with a protein to induce granuloma formation and release inflammatory molecules.

When the cells were pre-treated with XTMAB-16 at doses ranging from 1 microgram per milliliter (mcg/mL) to 40 mcg/mL, granuloma formation was significantly reduced in a dose-dependent manner compared with untreated cells. Release of inflammatory molecules was also inhibited when the cells were treated with XTMAB-16.

The effects of XTMAB at higher doses were comparable to those observed with the corticosteroid prednisone, Xentria said. Corticosteroids are often used to treat sarcoidosis, but can result in serious and significant side effects.

“While there are currently medications available to try to manage the symptoms of this rare disease, the available treatments have serious limitations, including limited efficacy and unacceptable side-effects, and there is a pressing need for better treatments,” Elliott D. Crouser, MD, professor of internal medicine at Wexner Medical Center at The Ohio State University, said. Crouser is also one of the study’s investigators.

The effectiveness of XTMAB-16 for reducing disease activity in humans will need to be determined in clinical trials, Xentria said.

Last year, Xentria announced a planned Phase 1 trial (NCT04971395) to evaluate the safety and tolerability of multiple XTMAB-16 doses in healthy volunteers. Secondary goals included pharmacokinetics — the therapy’s movement into, through and out of the body — immune reactions against the therapy, and disease biomarker levels.

The trial enrolled 25 adults, ages 18–45, who were randomly assigned to receive a single into-the-vein injection of XTMAB-16 (2 or 4 mg/kg) or a placebo. It was completed in March and the results are expected next year, according to Xentria.

The post Antibody-based Therapy Prevents Granuloma Formation in Cell Model appeared first on Sarcoidosis News.

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