In 2018, Or­chard Ther­a­peu­tics se­cured ac­cess to GSK’s pi­o­neer­ing gene ther­a­py for “bub­ble boy syn­drome,” Strimvelis, among a bas­ket of oth­er rare dis­ease pro­grams, af­ter the big British drug­mak­er de­cid­ed the slate of drugs was too niche for its ar­se­nal of treat­ments. Now, Or­chard has al­so elect­ed to steer away from “ul­tra-rare” dis­eases to pro­grams fo­cused on more preva­lent con­di­tions.

The strate­gic shift, which al­so in­cludes halt­ing con­struc­tion of a Fre­mont man­u­fac­tur­ing fa­cil­i­ty and shut­ter­ing its Cal­i­for­nia R&D fa­cil­i­ty, has trig­gered a 25% cut in the com­pa­ny’s work­force.

“In our view, the new busi­ness plan rep­re­sents a smart repri­or­i­ti­za­tion of its com­mer­cial strat­e­gy to fo­cus on high­er yield op­por­tu­ni­ties and con­serve cash. This should re­move any need for near-term fi­nanc­ings,” Cowen’s Yaron Wer­ber wrote in a note.

Bob­by Gas­par

The Lon­don, Boston, and San Fran­cis­co-based biotech — which went pub­lic in 2018 in a bumper $200 mil­lion IPO — has a port­fo­lio of ex vi­vo gene ther­a­pies, in which a pa­tient’s stem cells are ex­tract­ed and tweaked out­side the body be­fore be­ing trans­plant­ed back in, with the aim to treat a va­ri­ety of rare im­mune and meta­bol­ic dis­eases. Founder and now chief Bob­by Gas­par was heav­i­ly in­volved in the de­vel­op­ment of these hematopoi­et­ic stem cell gene ther­a­pies, bring­ing them from some of the first stud­ies in pa­tients to po­ten­tial reg­u­la­to­ry ap­provals.

GSK took a near­ly 20% stake in Or­chard in 2018, in re­turn for Strimvelis and oth­er gene-ther­a­py pro­grams. Strimvelis was one of the few ap­proved gene ther­a­pies in 2016, but up­take in the rare pa­tient pop­u­la­tion for adeno­sine deam­i­nase se­vere com­bined im­mun­od­e­fi­cien­cy (ADA-SCID) had strug­gled — the ther­a­py had on­ly been used in a hand­ful of pa­tients by 2018. In its IPO prospec­tus, Or­chard had stressed that the ther­a­py’s prod­uct rev­enue would not be enough to make the com­pa­ny prof­itable. Be­sides, Or­chard was al­so de­vel­op­ing its own ACA-SCID gene ther­a­py, OTL-101.

On Thurs­day, Or­chard said it was re­duc­ing in­vest­ment in OTL-101 and OTL-300 (its trans­fu­sion-de­pen­dent be­ta-tha­lassemia pro­gram) — to pour its re­sources in­to its pro­grams for metachro­mat­ic leukody­s­tro­phy (OTL-200), Wiskott-Aldrich syn­drome (OTL-103), Mu­copolysac­cha­ri­do­sis type I (OTL-203) and Mu­copolysac­cha­ri­do­sis type II­IA, al­so known as San­fil­ip­po syn­drome type A (OTL-201). The com­pa­ny al­so un­veiled two new pre­clin­i­cal pro­grams in fron­totem­po­ral de­men­tia and Crohn’s dis­ease.

Or­chard’s US ap­pli­ca­tion to mar­ket OTL-200 may be de­layed, the com­pa­ny in­di­cat­ed on Thurs­day, as the FDA has raised ques­tions about the clin­i­cal end­points used, nat­ur­al his­to­ry da­ta and chem­istry man­u­fac­tur­ing and con­trol da­ta. The drug­mak­er plans to en­gage with the FDA this year to rem­e­dy these hic­cups be­fore mak­ing its sub­mis­sion, it said.

“As EMA raised sim­i­lar ques­tions about the clin­i­cal da­ta for OTL-200, man­age­ment is hope­ful that they have the da­ta that FDA is re­quest­ing. How­ev­er, as the meet­ing with the FDA is un­like­ly to oc­cur un­til some time in H2:20, we an­tic­i­pate that the BLA fil­ing will get de­layed,” Wer­ber wrote.

If a new phase I/II study is re­quired, the BLA fil­ing could be de­layed, he said, post­pon­ing his ex­pect­ed launch to 2024 from 2022.

Or­chard’s cash, cash equiv­a­lents and in­vest­ments as of March 31 were $263.9 mil­lion. The re­or­ga­ni­za­tion an­nounced on Thurs­day, which gen­er­at­ed cash sav­ings of ap­prox­i­mate­ly $125 mil­lion through the end of 2021, will ex­tend the com­pa­ny’s abil­i­ty to keep the lights on in­to 2022.

So­cial: Bob­by Gas­par, Or­chard CEO (Roy­al Col­lege of Pae­di­atrics and Child Health, YouTube)

Treatment of early Alzheimer’s patients with Biogen’s new drug Aduhelm should closely resemble how the drug was studied in its pivotal clinical trials, according to new recommendations from a panel of neuroscience experts led by UNLV’s Jeffrey Cummings.

“Those considering aducanumab therapy should understand that the expected benefit is slowing of cognitive and functional decline; improvement of the current clinical state is not anticipated,” they wrote Tuesday in The Journal of Prevention of Alzheimer’s Disease, noting that some of their recommendations are more specific or more restrictive than the information provided in the FDA’s prescribing information.