Antios Therapeutics has completed the Phase 1b clinical trial of ATI-2173, an Active Site Polymerase Inhibitor Nucleotide (ASPIN), in patients with chronic hepatitis B virus (HBV) infection.

“Despite the availability of a vaccine, HBV remains a serious global public health problem with more than 250 million people worldwide living with chronic infection,” said Gregory Mayes, chief executive officer of Antios. “Life-long treatment with nucleoside analogues can control the infection by suppressing viral replication, but it rapidly rebounds in most patients when medication is stopped. ATI-2173’s unique mechanism of action positions it as a promising clinical candidate and potential backbone treatment in a functional curative regimen for chronic HBV infection. We look forward to presenting the data to the scientific community at an upcoming medical conference.”

The placebo-controlled Phase 1b trial evaluated the safety, tolerability, pharmacokinetics, and measurable reductions in HBV viral load of multiple oral doses of ATI-2173 in 24 patients with chronic HBV infection. The patients were randomized 6:2 to three dose cohorts: 10 mg, 25 mg or 50 mg of ATI-2173 or placebo, dosed orally, once-daily for 28 days. All doses were generally well tolerated with no apparent dose relationship for occurrence of adverse events, and no serious adverse events were observed. Based on the potent viral response observed, the 25 and 50 mg doses have been selected for the next clinical study that is expected to start in early 2021.

ATI-2173 is a novel, orally-administered, liver-targeted Active Site Polymerase Inhibitor Nucleotide (ASPIN) molecule designed to deliver the 5’-monophosphate of clevudine to the liver. This L-nucleoside’s active 5’-triphosphate has unique antiviral properties as a non-competitive, non-chain terminating HBV polymerase inhibitor that distorts the active site of HBV polymerase resulting in potent HBV antiviral activity and extended off-treatment suppression of HBV DNA. ATI-2173 targets the liver, delivering high levels of the unique 5’- triphosphate while limiting systemic exposure to the parent L-nucleoside. ATI-2173 has the potential to become an integral part of a curative combination regimen for chronic hepatitis B.