FDA clears clinical study of ZKN-013 in healthy volunteers

Therapy binds to ribosomes, letting protein-making machinery generate functional protein

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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The U.S. Food and Drug Administration (FDA) has approved a clinical trial in healthy volunteers of ZKN-013, a treatment candidate for recessive dystrophic epidermolysis bullosa (RDEB) and junctional epidermolysis bullosa (JEB).

Developed by Eloxx Pharmaceuticals, ZKN-013 is an oral therapy that can overcome nonsense mutations, a type that causes a premature stop signal in the gene sequence, resulting in a shorter, usually nonfunctional protein. According to Eloxx, nonsense mutations represent 30-40% of all mutations in the COL7A1 gene, which cause RDEB, and 70% of all mutations in LAMB3, one of the genes in which mutations result in junctional epidermolysis bullosa (JEB).

“FDA clearance to begin our planned single ascending dose trial is an important milestone toward providing a potential treatment option for patients with RDEB and JEB,” Sumit Aggarwal, president and CEO at Eloxx, said in a press release.

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How does ZKN-013 work?

ZKN-013 works by binding to ribosomes — structures where proteins are produced in cells — letting the protein-making machinery generate a full-length, functional protein.

The therapy was designed through the TURBO-ZM platform, a technology for rapidly synthesizing ribosomal modulating agents (RMAs) with a lower size and are more soluble in water. It enables potential therapies to be orally and chronically delivered, and to modulate protein production, according to the company’s website.

“ZKN-013, our lead TURBO-ZM based molecule, is the first program developed from hit to lead and is now poised to enter clinical development,” Aggarwal said.

In preclinical studies in skin cells derived from people with RDEB caused by nonsense mutations, ZKN-013 was able to restore functional type VII collagen production in a dose-dependent way. Type VII collagen is the protein coded by the COL7A1 gene and plays a key role in connecting the different layers of the skin, anchoring them to each other.

According to Eloxx, preclinical work supports safe oral dosing of RMAs at 300-400 mg every day.

The clinical trial will test a single ascending dose (SAD) of ZKN-013 in healthy volunteers. This type of study typically aims to determine a treatment’s safe dose range and side effects.

After its completion and a discussion with the FDA, further SAD and multiple ascending dose (MAD) tests are expected. The MAD testing could include participants with RDEB due to the high benefit/risk in patients, as cited by the FDA.