#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.

Con­quer­ing a silent killer: HDV and Eiger Bio­Phar­ma­ceu­ti­cals

Hepatitis delta, also known as hepatitis D, is a liver infection caused by the hepatitis delta virus (HDV) that results in the most severe form of human viral hepatitis for which there is no approved therapy.

HDV is a single-stranded, circular RNA virus that requires the envelope protein (HBsAg) of the hepatitis B virus (HBV) for its own assembly. As a result, hepatitis delta virus (HDV) infection occurs only as a co-infection in individuals infected with HBV. However, HDV/HBV co-infections lead to more serious liver disease than HBV infection alone. HDV is associated with faster progression to liver fibrosis (progressing to cirrhosis in about 80% of individuals in 5-10 years), increased risk of liver cancer, and early decompensated cirrhosis and liver failure.
HDV is the most severe form of viral hepatitis with no approved treatment.
Approved nucleos(t)ide treatments for HBV only suppress HBV DNA, do not appreciably impact HBsAg and have no impact on HDV. Investigational agents in development for HBV target multiple new mechanisms. Aspirations are high, but a functional cure for HBV has not been achieved nor is one anticipated in the forseeable future. Without clearance of HBsAg, anti-HBV investigational treatments are not expected to impact the deadly course of HDV infection anytime soon.

No­var­tis is ax­ing 150 ear­ly dis­cov­ery jobs as CNI­BR shifts fo­cus to the de­vel­op­ment side of R&D

Novartis is axing some 150 early discover jobs in Shanghai as it swells its staff on the drug development side of the equation in China. And the company is concurrently beefing up its investment in China’s fast-growing biotech sector with a plan to add to its investments in local VCs.

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No­var­tis is eye­ing a multi­bil­lion-dol­lar Med­Co buy­out as Jer­sey biotech nears NDA — re­ports

To get from Novartis’ US headquarters to the Medicines Company, you make a left out of a square concrete building on NJ-Route 10, follow it past the sun orange veranda of Jersey’s Hot Bagels and the inexplicable green Vermont cabin that houses the Whippany Railway Museum until you turn right and immediately arrive at a rectangular glass building. It should take you about 12 minutes.

Reports are out that Novartis may be making that trip. Amid a torrent of Phase III data burnishing MedCo’s chances at a blockbuster cholesterol drug,  Bloomberg News is reporting that Novartis is looking to acquire the Jersey-based biotech.

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UP­DAT­ED: In a land­mark first glimpse of hu­man da­ta from Ver­tex, CRISPR/Cas9 gene ther­a­py sig­nals ear­ly ben­e­fit

Preliminary data on two patients with blood disorders that have been administered with Vertex and partner CRISPR Therapeutics’ gene-editing therapy suggest the technology is safe and effective, marking the first instance of the benefit of the use of CRISPR/Cas9 technology in humans suffering from disease.

Patients in these phase I/II studies give up peripheral blood from which hematopoietic stem and progenitor cells are isolated. The cells are tinkered with using CRISPR/Cas9 technology, and the edited cells — CTX001 — are infused back into the patient via a stem cell transplant. The objective of CTX001 is to fix the errant hemoglobin gene in patents with two blood disorders: beta-thalassemia and sickle cell disease, by unleashing the production of fetal hemoglobin.

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Badrul Chowdhury. FDA via Flickr

As­traZeneca los­es an­oth­er ex­ec­u­tive to biotech, as Badrul Chowd­hury moves to Savara

Another executive is migrating from the echelons of Big Pharma to the corridors of small biotech.

In April 2018, Badrul Chowdhury took his more than two decades of experience at the FDA to AstraZeneca, where he took on the role of senior vice president and chief physician-scientist for respiratory, inflammation and autoimmunity late-stage development in biopharmaceuticals R&D.

After about a year and a half in this role, Chowdhury is moving to a small Texas biotech called Savara, where he will serve as chief medical officer.

Yiannis Kiachopoulos and Artur Saudabayev, co-founders of Causaly

Lon­don AI up­start, which counts No­var­tis as a cus­tomer, can teach your com­put­er to read

When Amazon developed a machine-learning tool to make its recruitment process more efficient — the man-made system absorbed the gender-bias of its human makers, and the project was aborted. In the field of biopharmaceuticals, the way researchers train their machine learning algorithms can skew the outcome of predictions. But before those predictions can be made, the engine must learn to read to make sense of explosive volume of knowledge out there.

Burt Adelman. Novo Ventures

Here's a $25M seed fund aimed at back­ing some brash new drug ideas out of the Broad

As a former academic and a seasoned drug developer, Burt Adelman knew when he was recruited as a senior advisor to Novo Ventures in 2017 that one of his key priorities needs to be introducing the fund to the network he was so deeply embedded in.

“I was thinking long and hard on how can I, as a Boston insider, help Novo really get inside the ecosystem of Boston biotech?” he recalled in an interview with Endpoints News.

Welling­ton lines up a $393M bankroll for its next round of pri­vate biotech bets — and they’re like­ly think­ing big

Wellington Management made some uncustomary waves at the beginning of the year when it threw its considerable weight against Bristol-Myers Squibb’s $74 billion Celgene buyout. But after Bristol-Myers’ biggest investor conceded that game to the influential proxy firms involved, they’re now going to end the year by rolling out a big new investment fund for a new stable of fledgling biotechs on the private side of the industry.

As uter­ine race with Ab­b­Vie heats up, My­ovant eyes FDA ap­proval with tri­al re­sults from prostate can­cer

Myovant has long had a secret weapon in its uterine rivalry with AbbVie: Men.

While the small Swiss biotech has jockeyed with the Illinois-based giant for a foothold in the endometriosis and uterine fibroid therapy market, the company has been developing the same lead compound, relugolix, for use in one of the most common cancers for the uterus-less: prostate cancer. Today, Myovant is out with positive topline results from its big Phase III trial on the gonadotropin-releasing hormone (GnRH) antagonist. They say they’ve reached every primary and secondary endpoint with p values less than .0001.