Last fall, San­thera Phar­ma­ceu­ti­cals un­cer­e­mo­ni­ous­ly dumped a Duchenne pro­gram af­ter it flunked a Phase III tri­al, forc­ing a wave of lay­offs that trimmed the biotech’s staff from 120 to 40. Now, the Swiss com­pa­ny be­lieves it’s found a path to a come­back with a dif­fer­ent can­di­date in Duchenne.

San­thera re­vealed topline re­sults from a Phase IIb study for its va­morolone pro­gram, say­ing two dif­fer­ent dos­es each hit the pri­ma­ry end­point com­pared with place­bo. Tues­day’s da­ta give the biotech con­fi­dence to po­ten­tial­ly seek ap­proval for both dosage lev­els with the aim of sub­mit­ting an NDA in the first quar­ter of next year.

“This was the last thing that need­ed to fall in­to place for us to be, what I’m col­lo­qui­al­ly call­ing, San­thera 2.0,” CEO Dario Ek­lund told End­points News. “It’s re­al­ly a new start for the com­pa­ny.”

The news sent San­thera shares sky­rock­et­ing in the Swiss stock ex­change more than 60%.

Back in Oc­to­ber, San­thera was forced to halt a Phase III study for its now-de­funct idebenone pro­gram af­ter it failed an in­ter­im analy­sis. The com­pa­ny had been ramp­ing up for a po­ten­tial com­mer­cial launch through­out Eu­rope and had to with­draw its mar­ket­ing au­tho­riza­tion ap­pli­ca­tion from the EMA.

Most of the staffers laid off in the sub­se­quent re­struc­tur­ing were sta­tioned over­seas in more than half a dozen Eu­ro­pean mar­kets, Ek­lund said. The launch had been slat­ed for the first quar­ter of this year, but the re­sult­ing fail­ure forced San­thera to strip “down to the bones.”

Idebenone was de­signed to im­prove lung func­tion in pa­tients by en­er­giz­ing weak­ened mus­cle cells, and had long faced road­blocks in its de­vel­op­ment. The FDA re­ject­ed its orig­i­nal ap­pli­ca­tion for the pro­gram back in 2016 and asked for a con­fir­ma­to­ry tri­al — the tri­al that San­thera ter­mi­nat­ed last fall.

But the va­morolone can­di­date func­tions sim­i­lar to a steroid, which is the stan­dard of care for many Duchenne pa­tients. The Phase IIb study ex­am­ined dosage lev­els of 2 mg/kg per day and 6 mg/kg per day, look­ing at how 121 pa­tients’ time to stand from a supine po­si­tion was short­ened af­ter 24 weeks of treat­ment.

In the high dose, pa­tients re­duced their time to stand from 6 sec­onds to 4.6 sec­onds, while the place­bo group went from 5.4 to 5.5 sec­onds. That equat­ed to a sparkling p-val­ue of p=0.002. San­thera didn’t re­veal the time dif­fer­ence for the low­er dose, but re­port­ed a p-val­ue here of p=0.02. There were “sub­tle dif­fer­ences” in the dose re­spons­es, va­morolone pro­gram lead Shabir Hasham told End­points.

Ide­al­ly, San­thera wants both dos­es to be ap­proved so that pa­tients have the op­tion of down-titrat­ing from the high­er lev­el if they ex­pe­ri­ence side ef­fects. There were no treat­ment-re­lat­ed side ef­fects that reg­is­tered at grade 3 or high­er, but Hasham said about one-third of tri­al par­tic­i­pants in the high­er dose group moved down to the low­er dose.

“Pa­tients can start on a high­er-dose ther­a­py, and those who are com­fort­able can stay while oth­ers come down and don’t lose the ef­fi­ca­cy,” Hasham said. “That’s re­al­ly the unique thing.”

Con­ver­sa­tions with reg­u­la­tors will dic­tate how San­thera ul­ti­mate­ly moves for­ward, Ek­lund said. He hopes that be­cause the can­di­date is an oral so­lu­tion rather than a pill, San­thera’s pitch will prove per­sua­sive — par­tic­u­lar­ly giv­en how typ­i­cal cor­ti­cos­teroid treat­ments used for Duchenne can be down-titrat­ed in a sim­i­lar man­ner.

Last Sep­tem­ber, San­thera picked up glob­al rights to va­morolone from Rever­a­Gen af­ter sign­ing on to the op­tion a few years ago. The com­pa­ny is look­ing to aug­ment the Phase IIb da­ta with re­sults from a pre­vi­ous­ly-re­port­ed Phase IIa study, which Hasham said now shows safe­ty and tol­er­a­bil­i­ty of the pro­gram over 30 months.

89bio said its drug was better than placebo at lessening fibrosis without worsening nonalcoholic steatohepatitis, or NASH, in two of three dose groups.

The San Francisco biotech said it thinks the Phase IIb data pave the way for a potential Phase III, following in the footsteps of another biotech in its drug class, Akero Therapeutics. To fund a late-stage study, CEO Rohan Palekar told Endpoints News 89bio “would need to raise additional capital,” with the company having about $188 million at the end of last year.