Ver­tex and CRISPR Ther­a­peu­tics un­veil more pos­i­tive gene ther­a­py da­ta, but busul­fan again casts a shad­ow over the field

Less than 12 hours af­ter re­veal­ing a flop on its sec­ond shot for al­pha-1 an­tit­rypsin de­fi­cien­cy, Ver­tex plowed ahead with an­oth­er da­ta drop from its part­ner­ship with CRISPR Ther­a­peu­tics. And though the topline proved pos­i­tive, con­cerns over con­di­tion­ing agents con­tin­ue to linger over the col­lab­o­ra­tion, as well as the en­tire gene ther­a­py space.

Pre­sent­ing da­ta from two tri­als at the Eu­ro­pean Hema­tol­ogy As­so­ci­a­tion an­nu­al meet­ing, the pair an­nounced that fol­low-up da­ta of at least three months for 22 pa­tients with ge­net­ic blood dis­or­ders in­di­cat­ed a “con­sis­tent and sus­tained” re­sponse to the ex­per­i­men­tal drug CTX001. All 15 pa­tients with trans­fu­sion-de­pen­dent be­ta tha­lassemia did not need fur­ther blood trans­fu­sions and all sev­en with se­vere sick­le cell dis­ease were pain free, the biotechs an­nounced.

There was one pa­tient not in­clud­ed in the da­ta cut­off of March 30, how­ev­er, who ex­pe­ri­enced a cere­bel­lar he­m­or­rhage less than three months af­ter be­ing treat­ed. The se­ri­ous side ef­fect was re­lat­ed to the busul­fan con­di­tion­ing gene ther­a­py pa­tients un­der­go be­fore re­ceiv­ing treat­ment, Ver­tex said, and has since re­solved.

Busul­fan has long proved tricky for com­pa­nies de­vel­op­ing gene ther­a­pies, with the chemo reg­i­men prov­ing a nec­es­sary but in­ten­sive process for pa­tients. It’s been linked in the past to can­cer and some have linked it to po­ten­tial cas­es of leukemia and myelodys­plas­tic syn­drome seen in blue­bird bio’s gene ther­a­py stud­ies.

Ad­di­tion­al­ly, as Ver­tex and CRISPR had pre­vi­ous­ly re­vealed, one be­ta tha­lassemia pa­tient ex­pe­ri­enced four se­ri­ous side ef­fects re­lat­ed or pos­si­bly re­lat­ed to CTX001. They all oc­curred with­in the con­text of an in­flam­ma­to­ry re­sponse and have al­so re­solved.

In the be­ta tha­lassemia study, in­ves­ti­ga­tors fol­lowed the 15 pa­tients for a range of four to 26 months, and the sick­le cell pa­tients from five to 22 months. Sev­en from across both stud­ies are more than a year out since re­ceiv­ing treat­ment. Fri­day’s re­sults are an up­date to a da­ta cut from De­cem­ber’s ASH con­fer­ence, which had on­ly in­clud­ed 10 pa­tients.

The gene ther­a­py in ques­tion, be­ing de­vel­oped joint­ly by Ver­tex and CRISPR, is an au­tol­o­gous ex vi­vo CRISPR/Cas9 treat­ment. Ver­tex teamed up with CRISPR back in 2015, but the pair ex­pand­ed on their part­ner­ship in April in a bid to de­vel­op the treat­ment more quick­ly.

In the ex­pan­sion, Ver­tex paid an ad­di­tion­al $900 mil­lion cash to take an­oth­er 10% of fu­ture sales from the gene edit­ing ther­a­py, with CRISPR hand­ing over re­spon­si­bil­i­ty for com­mer­cial­iz­ing CTX001 in the US. Along with oth­er re­cent changes to their part­ner­ship, the move ef­fec­tive­ly hands Ver­tex re­spon­si­bil­i­ty for man­u­fac­tur­ing the ther­a­py and stew­ard­ing it past reg­u­la­tors across the globe.

Should CTX001 be­come the first CRISPR-based ther­a­py to hit the mar­ket, that wa­ger would give Ver­tex a sig­nif­i­cant sales ad­van­tage over ri­vals like blue­bird. The Nick Leschly-run com­pa­ny has faced an up­hill climb for its gene ther­a­py pro­grams, ul­ti­mate­ly split­ting it­self in­to two com­pa­nies at the be­gin­ning of the year.

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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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.”

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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Hal Barron, GSK R&D chief (Endpoints News)

Hal Bar­ron gam­bles $625M cash on high-wire TIG­IT act, throw­ing Glax­o­SmithK­line in­to heat­ed race and com­plet­ing next-gen I/O trin­i­ty

Count Hal Barron and GlaxoSmithKline in for the TIGIT fight.

The stakes are as high as the risks: While a growing pack of Big Pharma rivals is lending credence to the hypothesis that TIGIT will be the next big immune checkpoint and cancer drug target, the first clinical trials have shown response rates that can be described as modest at best. But Barron’s bet is on the whole “axis” that the receptor sits on, with an eye on testing its new anti-TIGIT antibody not just in combo with PD-1 but also in triplets.

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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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