Preclinical safety data support ETX-312 for MASH human trials
E-therapeutics plans to seek approval this year for clinical trials
E-therapeutics announced positive preclinical toxicology data on ETX-312, its therapy for people with metabolic dysfunction-associated steatohepatitis (MASH), a severe form of fatty liver disease, and said it plans to submit an application for human trials by the end of the year.
“We look forward to advancing ETX-312 to first-in-human studies over the coming months and continuing to execute efficiently to offer a differentiated treatment option to MASH patients,” Ali Mortazavi, CEO of e-therapeutics, said in a company press release.
The company said it has had “productive interactions with regulatory authorities” that support its “clinical strategy and plans.”
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a form of fatty liver disease marked by abnormal accumulation of fat in the liver. Risk factors include high blood pressure, being overweight or obese, elevated blood fats, or high blood sugar or type 2 diabetes.
MASH is the progressive stage of MASLD, involving liver inflammation and damage, potentially leading to scarring (fibrosis), permanent scarring (cirrhosis), or liver cancer.
Proprietary platform
The company leveraged its HepNet computational platform, which incorporates artificial intelligence, to develop ETX-312, a so-called GalOmic small inhibitory RNA (siRNA) molecule.
siRNAs are small fragments of RNA that bind to specific messenger RNA (mRNA), an intermediate molecule derived from DNA that serves as a template for protein production. With siRNA binding, the mRNA is broken down, thus lowering the production of the target protein.
GalOmic siRNAs like ETX-312 are modified with a molecule called N-acetylgalactosamine, or GalNAc, which helps deliver the therapy directly to liver cells.
The experimental therapy is specifically designed to lower the production of an undisclosed liver protein the company discovered as a potential therapeutic target for MASH. It also has the potential for subcutaneous (under-the-skin) administration every three months.
In preclinical studies using a diet-induced MASH mouse model, ETX-312 lessened disease activity, reduced liver inflammation, and slowed the progression of fibrosis, according to e-therapeutics. The therapy was effective alone or in combination with approved and experimental treatments.
Newly announced results concern animal toxicology studies required by regulators before testing in human patients. According to the company, data showed that doses exceeding anticipated clinical exposures were well tolerated, with no adverse findings.
The company also said it manufactured a clinical batch of ETX-312 in advance of human testing under Good Manufacturing Practice guidelines, which ensure that drugs meet the appropriate quality standards before being used in humans.
“Recent results and progress on ETX-312 represent a pivotal step towards the clinical development of our first GalOmic therapeutic, designed to silence a novel target identified in-house,” Mortazavi said. “The tolerability profile of ETX-312 provides key de-risking for our program,” supporting a clinical trial application filing in the fourth quarter, he said.
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