Or­chard Ther­a­peu­tics prunes jobs to re­fo­cus pri­or­i­ties on big­ger fruit

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)

Biogen CEO Michel Vounatsos (via Getty Images)

With ad­u­canum­ab caught on a cliff, Bio­gen’s Michel Vounatsos bets bil­lions on an­oth­er high-risk neu­ro play

With its FDA pitch on the Alzheimer’s drug aducanumab hanging perilously close to disaster, Biogen is rolling the dice on a $3.1 billion deal that brings in commercial rights to one of the other spotlight neuro drugs in late-stage development — after it already failed its first Phase III.

The big biotech has turned to Sage Therapeutics for its latest deal, close to a year after the crushing failure of Sage-217, now dubbed zuranolone, in the MOUNTAIN study.

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Pascal Soriot (AP Images)

As­traZeneca, Ox­ford on the de­fen­sive as skep­tics dis­miss 70% av­er­age ef­fi­ca­cy for Covid-19 vac­cine

On the third straight Monday that the world wakes up to positive vaccine news, AstraZeneca and Oxford are declaring a new Phase III milestone in the fight against the pandemic. Not everyone is convinced they will play a big part, though.

With an average efficacy of 70%, the headline number struck analysts as less impressive than the 95% and 94.5% protection that Pfizer/BioNTech and Moderna have boasted in the past two weeks, respectively. But the British partners say they have several other bright spots going for their candidate. One of the two dosing regimens tested in Phase III showed a better profile, bringing efficacy up to 90%; the adenovirus vector-based vaccine requires minimal refrigeration, which may mean easier distribution; and AstraZeneca has pledged to sell it at a fraction of the price that the other two vaccine developers are charging.

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Bahija Jallal (file photo)

TCR pi­o­neer Im­muno­core scores a first with a land­mark PhI­II snap­shot on over­all sur­vival for a rare melanoma

Bahija Jallal’s crew at TCR pioneer Immunocore says they have nailed down a promising set of pivotal data for their lead drug in a frontline setting for a solid tumor. And they are framing this early interim readout as the convincing snapshot they need to prove that their platform can deliver on a string of breakthrough therapies now in the clinic or planned for it.

In advance of the Monday announcement, Jallal and R&D chief David Berman took some time to walk me through the first round of Phase III data for their lead TCR designed to treat rare, frontline cases of metastatic uveal melanoma that come with a grim set of survival expectations.

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Jason Kelly, Ginkgo Bioworks CEO (Kyle Grillot/Bloomberg via Getty Images)

Af­ter Ko­dak de­ba­cle, US lends $1.1B to a syn­thet­ic bi­ol­o­gy com­pa­ny and their big Covid-19, mR­NA plans

In mid-August, as Kodak’s $765 million government-backed push into drug manufacturing slowly fell apart in national headlines, Ginkgo Bioworks CEO Jason Kelly got a message from his company’s government liaison: HHS wanted to know if they, too, might want a loan.

The government’s decision to lend Kodak three quarters of a billion dollars raised eyebrows because Kodak had never made drugs before. But Ginkgo, while not a manufacturing company, had spent the last decade refining new ways to produce materials inside cells and building automated facilities across Boston.

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Vivek Ramaswamy (Jeff Rumans/JPM 2020)

Urovan­t's lead drug dis­ap­points in mid-stage study as first big FDA de­ci­sion looms

Just as Urovant gets ready for its first big FDA decision on vibegron, the drug has flopped in what would’ve been a follow-on indication.

In a Phase IIa trial involving women with abdominal pain due to irritable bowel syndrome, vibegron failed to meet the bar on improving “average worst abdominal pain” over 12 weeks, compared to placebo, among IBS-D patients.

There were actually slightly more responders in the placebo group than in the drug arm, with only 40.9% of those randomized to vigebron achieving at least a 30% decrease in “worst abdominal pain” in the past 24 hours. The trial enrolled 222 women but only 189 completed the study.

Gen­mab ax­es an ADC de­vel­op­ment pro­gram af­ter the da­ta fail to im­press

Genmab $GMAB has opted to ax one of its antibody-drug conjugates after watching it flop in the clinic.

The Danish biotech reported Tuesday that it decided to kill their program for enapotamab vedotin after the data gathered from expansion cohorts failed to measure up. According to the company:

While enapotamab vedotin has shown some evidence of clinical activity, this was not optimized by different dose schedules and/or predictive biomarkers. Accordingly, the data from the expansion cohorts did not meet Genmab’s stringent criteria for proof-of-concept.

Vas Narasimhan, Novartis CEO (Jason Alden/Bloomberg via Getty Images)

Vas Narasimhan's 'Wild Card' drugs: No­var­tis CEO high­lights po­ten­tial jack­pots, as well as late-stage stars, in R&D pre­sen­ta­tion

Novartis is always one of the industry’s biggest R&D spenders. As they often do toward the end of each year, company execs are highlighting the drugs they expect will most likely be winners in 2021.

And they’re also dreaming about some potential big-time lottery tickets.

As part of its annual investor presentation Tuesday, where the company allows investors and analysts to virtually schmooze with the bigwigs, Novartis CEO Vas Narasimhan will outline what he thinks are the pharma’s “Wild Cards.” The slate of five experimental drugs are those that Novartis hopes can be high-risk, high-reward entrants into the market over the next half-decade or so, and cover a wide range of indications.

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The ad­u­canum­ab co­nun­drum: The PhI­II failed a clear reg­u­la­to­ry stan­dard, but no one is cer­tain what that means any­more at the FDA

Eighteen days ago, virtually all of the outside experts on an FDA adcomm got together to mug the agency’s Billy Dunn and the Biogen team when they presented their upbeat assessment on aducanumab. But here we are, more than 2 weeks later, and the ongoing debate over that Alzheimer’s drug’s fate continues unabated.

Instead of simply ruling out any chance of an approval, the logical conclusion based on what we heard during that session, a series of questionable approvals that preceded the controversy over the agency’s recent EUA decisions has come back to haunt the FDA, where the power of precedent is leaving an opening some experts believe can still be exploited by the big biotech.

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John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

Al­ny­lam gets the green light from the FDA for drug #3 — and CEO John Maraganore is ready to roll

Score another early win at the FDA for Alnylam.

The FDA put out word today that the agency has approved its third drug, lumasiran, for primary hyperoxaluria type 1, better known as PH1. The news comes just 4 days after the European Commission took the lead in offering a green light.

An ultra rare genetic condition, Alnylam CEO John Maraganore says there are only some 1,000 to 1,700 patients in the US and Europe at any particular point. The patients, mostly kids, suffer from an overproduction of oxalate in the liver that spurs the development of kidney stones, right through to end stage kidney disease.

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