China regulators OK Phase 1 trial of gene-editing therapy YOLT-201

FAP therapy shows 'promising' results in preliminary trial, company says

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by Steve Bryson, PhD |

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Regulatory authorities in China have authorized YolTech Therapeutics to launch a Phase 1 clinical trial testing YOLT-201, a one-time gene-editing therapy, in people with hereditary transthyretin (hATTR) amyloidosis, a group of conditions that includes familial amyloid polyneuropathy (FAP).

The approval from the National Medical Products Administration’s Center for Drug Evaluation clearing the Phase 1 trial “marks important progress in our team’s efforts in the field of in vivo gene editing,” Yuxuan Wu, founder and CEO of YolTech, said in a company press release.

In hATTR, inherited mutations in the TTR gene result in the buildup of an abnormal version of the TTR protein, which misfolds and forms clumps, called amyloid fibrils, that deposit in organs and tissues.

When amyloid fibrils accumulate in peripheral nerves — those that extend from the brain and spinal cord — the disease is called hATTR with polyneuropathy, or FAP. Its symptoms include numbness, tingling, or burning in the limbs and extremities. Amyloid deposits also can build up in the heart and cause damage, resulting in a related condition called hATTR with cardiomyopathy.

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Phase 1 trial will test various doses, early efficacy of YOLT-201

Given as a one-time infusion directly into the bloodstream, YOLT-201 uses the CRISPR gene-editing system to alter the TTR gene and stop the production of the TTR protein. Lipid nanoparticles, or small vesicles made up of fatty molecules, deliver the therapy directly to liver cells, where the TTR protein is made.

YolTech noted that a single dose of YOLT-201 safely and sustainably reduced TTR protein levels in the bloodstreams of nonhuman primates.

The first adult patient with hATTR-cardiomyopathy was dosed late last year in an open-label, dose-escalation, investigator-initiated Phase 1 trial (NCT06082050), the company announced in a December press release. So far, the therapy has significantly decreased TTR protein levels, with no signs of serious adverse events, according to the company.

YOLT-201 “has achieved promising preliminary efficacy and safety results in the investigator-initiated trial,” Wu said. “Patients treated with YOLT-201 showed a significant decrease in TTR levels,” with no dangerous adverse reactions during treatment or follow-up, he said.

The new multicenter, open-label Phase 1/2a trial, dubbed YT-YOLT-201-101, will involve people with either FAP or hATTR-cardiomyopathy.

[YOLT-201] has achieved promising preliminary efficacy and safety results in the investigator-initiated trial.

The first stage will test single and escalating doses of YOLT-201 to determine the optimal dose, while the second stage will be a dose-expansion phase to assess the therapy’s preliminary efficacy.

Researchers will also evaluate the therapy’s safety and tolerability, along with its pharmacokinetics — that is, how it moves into, through, and out of the body — and pharmacodynamics, or its effect on the body.

“We are confident to advance YOLT-201 clinical trials and committed to providing innovative treatment solutions for patients,” Wu said.