Metagenomi aiming for clinical trials of gene-editing therapy in 2026
Developer's MGX-001 for hemophilia A now being tested in animal study
Metagenomi is now working on preclinical studies to advance MGX-001, its experimental gene-editing therapy for hemophilia A, with the goal of bringing the treatment candidate into clinical trials in 2026.
As part of a corporate update also noting 2024 progress, Metagenomi announced that, this year, it will be concluding a study testing MGX-001 in nonhuman primates. The company also will be carrying on with work that aims to support applications seeking regulatory permission to start testing the therapy in people with hemophilia A in the U.S. and other countries.
If all goes well, Metagenomi said it is hoping to submit applications and start testing MGX-001 in patients in 2026.
“Our vision at Metagenomi is to create curative genetic medicines for patients by harnessing the power of our metagenomics platform,” Brian C. Thomas, PhD, CEO and founder of Metagenomi, said in a company press release. According to the company, metagenomics is the study of genomes — a genome is the complete set of genetic information in an organism — “recovered from uncultivated organisms in the natural environment.”
“We made tremendous progress toward this goal in 2024, with accomplishments including substantially advancing MGX-001, our potentially curative development candidate for hemophilia A. … Building on this momentum, we look forward to significant additional milestones for Metagenomi in 2025 as we progress our wholly-owned and partnered programs toward the clinic,” Thomas said.
Gene-editing therapy aims to deliver healthy F8 gene copy to patients
Hemophilia A is caused by mutations in the F8 gene, which provides instructions to make clotting factor VIII, or FVIII, a protein needed for normal blood clotting. In hemophilia A, the lack or dysfunction of FVIII compromises the blood’s ability to clot normally, leading to the unusually common and prolonged bleeding episodes that characterize the disorder.
A gene-editing therapy, MGX-001 aims to deliver a healthy copy of the F8 gene to cells in the liver, where most clotting factors are produced. By delivering a working version of the gene to liver cells, the therapy ultimately aims to restore the body’s ability to produce functional FVIII and normalize blood clotting.
MGX-001 delivers the therapeutic F8 gene using a modified version of a virus, called adeno-associated virus or AAV, that’s been engineered to carry the therapeutic gene instead of causing harmful infections. At the same time, MGX-001 also uses lipid nanoparticles — small vesicles made up of fatty molecules — to deliver a guide RNA and a nuclease to cells.
A nuclease is an enzyme that’s able to cut a cell’s DNA. The guide RNA, as the name implies, works to guide the nuclease to make a cut at a specific location in the genome. In the case of MGX-001, it specifically guides the enzyme to make a cut in the gene encoding albumin, a blood protein that’s made in large quantities by the liver. The goal is to insert the healthy F8 gene into the existing albumin gene of some liver cells, prompting them to produce FVIII at the same high levels that they normally produce albumin.
Preclinical data announced so far demonstrated that this approach sustainably increased FVIII activity in nonhuman primates for longer than 16 months.
In 2024, the company had initial discussions with U.S. regulators regarding the gene-editing therapy, per the release. As an “anticipated milestone” for 2026, Metagenomi is seeking to “advance MGX-001 into first-in-human studies,” the company noted.
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