#ASH17: Blue­bird touts ear­ly signs that its new-and-im­proved sick­le cell gene ther­a­py is work­ing

Blue­bird bio $BLUE says they’ve been able to gath­er ev­i­dence to help prove that their new-and-im­proved ap­proach to mak­ing a gene ther­a­py for sick­le cell dis­ease has the po­ten­tial to be a con­sis­tent­ly ef­fec­tive once-and-done ther­a­py.

Fol­low­ing up on some dis­ap­point­ing ev­i­dence of in­con­sis­ten­cy among the first small group of pa­tients treat­ed with Lenti­Glo­bin, blue­bird’s team went back to the draw­ing board to whip up a new ap­proach to man­u­fac­tur­ing that they be­lieved would over­come their ini­tial set­back.

Two pa­tients — 1312 and 1313 — were treat­ed us­ing the re­fined process as least once. (The first was treat­ed twice, first us­ing the old and then the new ap­proach.) Their ex­pe­ri­ences will be spot­light­ed at the up­com­ing ASH meet­ing in ear­ly De­cem­ber, with up­dates com­ing on their re­sponse.

Mo­hammed As­mal

It takes a step in a di­rec­tion we feel is quite pos­i­tive,” says Mo­hammed As­mal, blue­bird’s VP of clin­i­cal de­vel­op­ment.

That mes­sage helped stoke a 15% in­crease in the biotech’s share price.

The re­al proof will come when re­searchers have a chance to see if bet­ter cell en­graft­ment al­lows these pa­tients to pro­duce nor­mal red blood cells, po­ten­tial­ly cur­ing the ail­ment.

It was clear ear­ly on among the first group of pa­tients that there was an en­graft­ment prob­lem, says blue­bird CEO Nick Leschly. So they de­cid­ed to take a new course. First, they took ac­tion to bat back the in­flam­ma­tion and oth­er prob­lems that oc­curred in pa­tients’ bone mar­row, giv­ing them bet­ter stem cells to work with. Then they used a new man­u­fac­tur­ing process — to be high­light­ed at ASH — that gave them a much high­er vec­tor copy num­ber to work with, im­prov­ing the odds of suc­cess.

That was clear­ly ap­par­ent in the first pa­tient, who was first treat­ed with a ther­a­py made from the first ap­proach, fol­lowed by more ef­fec­tive treat­ment in the sec­ond.

Nick Leschly

“The copy num­ber was (ini­tial­ly) in a range of .3, .5 to 1,” says the CEO. “Now you look across, and we’re now in the range of 2 to 3.” And he adds: “The num­ber of cells mod­i­fied is dra­mat­i­cal­ly dif­fer­ent.”

To be sure, it’s a small num­ber of pa­tients to re­view, but in sick­le cell dis­ease small num­bers can be com­pelling. And blue­bird has lots of rea­sons to tout a new, more ef­fec­tive ther­a­peu­tic ap­proach af­ter stum­bling ear­ly on, rais­ing doubts about their abil­i­ty to beat out oth­er ther­a­pies now in the clin­ic.

That’s what they will be dis­cussing at ASH as they prep for more work with a new batch of pa­tients who will be in­volved in the piv­otal work ahead.

In­side Track: Be­hind the Scenes of a Ma­jor Biotech SPAC

Dr. David Hung and Michelle Doig are no strangers to the SPAC phenomenon. As Founder and CEO of Nuvation Bio, a biotech company tackling some of the greatest unmet needs in oncology, Dr. Hung recently took the company public in one of this year’s biggest SPAC related deals. And as Partner at Omega Funds, Doig not only led and syndicated Nuvation Bio’s Series A, but is now also President of the newly formed, Omega-sponsored, Omega Alpha SPAC (Nasdaq: OMEG; oversubscribed $138m IPO priced January 6, 2021).

Barry Greene, Sage CEO

UP­DAT­ED: Sage's sec­ond chance at de­pres­sion hits the PhI­II pri­ma­ry, but ques­tions re­main over dura­bil­i­ty, side ef­fects

Looking to make a comeback after a big Phase III flop, Sage Therapeutics revealed data they believe could change the entire depression treatment landscape, given the vast array of failures in the field. But some results are spooking investors, sending Sage $SAGE shares down early Tuesday.

First, the primary: Sage and Biogen reported Phase III data for once-daily zuranolone Tuesday morning, saying the experimental drug hit its primary endpoint by spurring a statistically significant change from baseline in the 17-item Hamilton Rating Scale for Depression total score. After 15 days, patients in the drug arm saw an average change of -14.1 points, compared to -12.3 on placebo.

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Bio­gen sig­nals a big PhI­II fail­ure as the lead gene ther­a­py in their $800M Night­star buy­out goes down in flames

That $800 million buyout of Nightstar has turned into a bust for Biogen as the lead therapy in the deal failed a pivotal study, signaling a severe setback for the biotech’s ambitions in gene therapies.

The big biotech put out the word after the market closed on Monday that the gene therapy they picked up in the deal for a degenerative blindness called choroideremia failed the Phase III study, just a month after their #2 drug in the deal also flopped in a mid-stage study.

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Michel Sade­lain puts his name and new cell en­gi­neer­ing tech be­hind 'ag­nos­tic' CAR-T start­up chas­ing epi­ge­net­ic anti­gens

It felt natural for Alain Maiore and Sebastian Amigorena to bring in Michel Sadelain as a co-founder of Mnemo Therapeutics. A CAR-T pioneer, Sadelain had been involved as an advisor since the early days — enthusiastic about Amigorena’s work in a genetic knockout that could enhance T cell memory and a new class of potential targets he’s discovered — and could introduce some well-known technologies to the toolbox. So they got the initial cash from Sofinnova Partners to plant roots in Paris and New York in early 2019; within a few months, they began to see more clearly just what the antigen discovery platform might unlock.

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CEO Harith Rajagopalan (Fractyl)

Af­ter a decade in the type 2 di­a­betes game, Fractyl Lab­o­ra­to­ries recharges with a fresh $100M and a new name

Harith Rajagopalan compared the way type 2 diabetes is managed to sticking your fingers in a dam that’s leaking from a number of places.

You can take drugs to lower your blood sugar, cholesterol, or blood pressure, but you’re not addressing what he says is the core issue — the metabolic abnormality that causes the disease.

“We’re so busy plugging the holes in the dam, we don’t have time to see that the whole infrastructure is at risk,” he said. “That infrastructure is a full-body systemic metabolic abnormality called metabolic syndrome, that we’re ignoring while we’re so busy trying to treat all of the individual symptoms of the condition.”

Geoffrey Porges, SVB Leerink

Top an­a­lyst maps a rocky road for Ver­tex — un­less they adopt a $10B M&A cam­paign to save the pipeline

After repeatedly poking Vertex $VRTX execs with pointed criticism of their R&D strategy, top SVB Leerink analyst Geoffrey Porges is now turning up the heat to a full-scale roasting.

In a note out early Monday morning, Porges spotlights the impact of Vertex’s recent follow-up failure on AATD — their treatment hit the endpoint but missed on commercial prospects — rewriting his recommended scenario for CEO Reshma Kewalramani as she grapples with the setback.

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Alexander Vos, VectorY CEO

Start­ing fresh in man­u­fac­tur­ing, For­bion start­up re­fu­els to steer next-gen gene ther­a­py ap­proach for ALS, Alzheimer's in­to clin­ic

Forbion laid out its case for a next-generation gene therapy approach when it took the wraps off VectorY Therapeutics and its vectorized antibody tech in February. Now, the Dutch VC has tapped an experienced hand at cell and gene therapy manufacturing to steer the ship — and pulled a marquee syndicate for a €31 million ($37.6 million) seed round.

Alexander Vos, the new CEO, is a venture partner at BioGeneration Ventures and jumps immediately from VarmX, a BGV portfolio company developing an anticoagulant. But before that, he had led Dutch CDMO PharmaCell for eight years until it was bought out by Lonza.

Lynn Fitch, Mississippi Attorney General (Rogelio V. Solis/AP Images)

Mis­sis­sip­pi sues Eli Lil­ly, Sanofi and No­vo over in­sulin prices as in­ter­change­able biosim­i­lars may ar­rive soon

Mississippi Attorney General Lynn Fitch last week sued the top three insulin manufacturers, which collectively cover almost the entire US insulin market, alleging that they’ve colluded to raise their prices in lockstep, and in some cases by more than 1,000% for drugs that are decades old.

“Because of Manufacturer Defendants’ collusive price increases, nearly a century after the discovery of insulin, diabetes medications have become unaffordable for many diabetics,” the lawsuit says.

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Andrew Hopkins, Exscientia CEO

Ex­sci­en­tia spends Soft­Bank's cash in bid to edge out AI ri­vals

Exscientia is sprinting to win the great AI biotech race.

The UK company, having long labored on small discovery deals with large pharmas, raised up to $525 million in a Series D led by the infamous Japanese conglomerate SoftBank in April and followed it up less than a month later with a Bristol Myers Squibb deal that paid $50 million cash and $1.2 billion in milestones.

Now, the Oxford spinout is splurging on a shiny new tool. On Monday they announced they purchased the three-year-old molecule-screening biotech Allcyte, a longtime collaborator, for $60.6 million in cash and stock.

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