While hepatitis B virus (HBV) infection is avoidable with a vaccine, a host of companies are searching for a cure for the hundreds of thousands in the US who already have it. Antios Therapeutics threw its hat in the ring three years ago, and on Monday closed a $96 million crossover round to see its lead program through Phase II.
When asked if an IPO is on the horizon, CEO Greg Mayes said: “We’re going to be prepared for one, yes.”
Antios launched back in 2015 with $25 million in Series A funding and a goal to form the “backbone” of a curative regimen for chronic HBV. It was founded by Abel De La Rosa, a former executive at hep C pioneer Pharmasset, and CMO Doug Mayers, who hailed from Idenix. Mayes took the helm back in December after De La Rosa retired.
When it comes to tackling HBV, Mayers says there are two “philosophical camps.” One is to boost immunity using vaccinations, TLR inhibitors or siRNAs. The second is to shut the virus down completely so the normal immune system can clear it out. Antios is part of the latter.
The company’s lead candidate, dubbed ANT-2173, is an active site polymerase inhibitor Nucleotide (ASPIN) derived from an old Pharmasset drug called clevudine. While currently approved treatments, like tenofovir and entecavir, control viral replication, the effect quickly wanes after treatment is stopped. Antios’s approach is to inhibit viral replication one polymerase at a time, versus one genome at a time, potentially giving patients the ability to safely withdraw treatment.
ANT-2173 had “potent on-treatment and durable off-treatment effects” as a monotherapy in a Phase Ib study, according to Antios. Mayes said the company will provide more detailed results in June. The candidate is currently in a Phase IIa study in combination with tenofovir, and is expected to enter Phase IIb by mid-2022.
“The three arms that we’re currently doing will be completed this year,” Mayers said of the Phase IIa. “We could continue adding arms to that study to explore novel mechanisms or novel strategies. So I’m not sure that it’s going to end anytime soon. It may become our development platform for the company to explore combinations with other companies.”
Clevudine started out at Bukwang, before it was licensed to Triangle Pharmaceuticals in 1998. After buying out Triangle in 2003, Gilead transferred the rights back to Bukwang, which then licensed the candidate to Pharmasset two years later.
Pharmasset ended up discontinuing the program after 1% of patients in a Phase III trial developed reversible proximal skeletal muscle myopathy at the one-year mark.
Antios says ANT-2173 should avoid those effects because it’s targeted to the liver. With the original formulation, there was a “bolus of clevudine” that the kidneys would have to clear out, Mayers said.
“With our drug it’s very slowly released from the liver over 24 hours, the kidneys handle it much more efficiently, so we’re dropping the exposure to clevudine very significantly, and so we get more potency, much lower clevudine exposure is in the blood, and we think that by limiting our treatment to one year… we should drop the risk of myopathy well below the 1% that was originally seen,” he said.
Antios is up against a host of companies hunting for an HBV cure, including Vir Biotechnology, which read out Phase I data back in January that were so promising they even surprised the CMO. Assembly Biosciences’ attempt flopped in a Phase II trial in November. In August, GlaxoSmithKline showcased the proof-of-concept data that convinced it to exercise the option on Ionis’ hepatitis B treatments. But J&J and Arrowhead are rushing to beat it, as well as Roche, which signed up to develop Dicerna’s drug.