Arbutus Biopharma is officially canning its RNA-destabilizing hepatitis B program due to safety concerns found in preclinical studies carried out in two species. The move comes four months after the company delayed the treatment’s phase 1 study to look more deeply into its safety profile.
“After reviewing all the data from the preclinical studies, and in consultation with external regulatory and pre-clinical experts, we have decided to not move AB-452 forward,” said Arbutus Chief Scientific Officer Michael Sofia, Ph.D., in a statement.
Though AB-452 didn’t pan out, the company isn’t giving up on the RNA destabilizer mechanism of action, Sofia said, adding it could potentially lead to an oral treatment. The plan is to go after next-generation compounds that destabilize and ultimately, break down, hepatitis B virus RNA.
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Just before postponing the drug’s entry to the clinic, Arbutus dumped its Roivant-backed hepatitis B program after two healthy people in a phase 1 study developed acute hepatitis—the very disease the drug was supposed to treat.
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The company was developing the drug, an oral capsid inhibitor called AB-506, for the treatment of chronic hepatitis B, where patients can’t clear the virus after six months. It was designed to attack the capsid, or protein shell, that protects the virus’ genetic material, thereby blocking viral replication. Despite the flop, Arbutus isn’t abandoning capsid inhibitors either.
“[We] have a number of oral follow-on capsid inhibitor compounds with distinct chemical scaffolds that we believe have the potential to contribute to the inhibition of HBV replication as part of a combination regimen,” Sofia said at the time.
Now, Arbutus is focusing on AB-729, an RNAi drug injected just under the skin, and AB-836, a next-generation capsid inhibitor to replace AB-506. The former is in a phase 1a/1b study in healthy volunteers, as well as people with chronic hepatitis B infection. The company expects to wrap IND-enabling studies for the latter by the end of the year.