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.

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