Just in time to as­sure a de­ci­sion be­fore CVR dead­line, Bris­tol My­ers Squibb files NDA for Cel­gene/blue­bird CAR-T

A new CAR-T ther­a­py may be com­ing. And maybe $9 per share for Cel­gene in­vestors, too.

Bris­tol My­ers Squibb an­nounced they sub­mit­ted an NDA for the mul­ti­ple myelo­ma “ide-cel” CAR-T ther­a­py Cel­gene de­vel­oped in part­ner­ship with blue­bird. The ther­a­py is one of the three that has to be ap­proved to un­lock the BMS-Cel­gene con­tin­gent val­ue agree­ment that would give share­hold­ers of the ab­sorbed NJ com­pa­ny $9 per share. The first, ozan­i­mod, was ap­proved last week. The sec­ond, a CAR-T treat­ment for non-Hodgkin’s lym­phoma called liso-cel, was sub­mit­ted to the FDA in De­cem­ber.

As Mizuho’s Sal­im Syed point­ed out in a note to in­vestors, the tim­ing is not ran­dom. The March 31 sub­mis­sion means that even un­der stan­dard re­view, the FDA will is­sue a de­ci­sion by March 31, 2021, the dead­line for ap­proval un­der the con­tin­gent val­ue agree­ment.

Strong num­bers bol­ster BMS’s sub­mis­sion. At ASH in De­cem­ber, they re­leased Phase II da­ta show­ing that in 140 pa­tients with re­lapsed and re­frac­to­ry mul­ti­ple myelo­ma, around three quar­ters re­spond­ed and around a third showed a com­plete re­sponse. In the most ef­fec­tive dos­ing arm, 81.5% re­spond­ed and 35.2% went in­to com­plete re­mis­sion. The me­di­an du­ra­tion was 11.3 months.

BMS isn’t alone in the hunt, al­though they are for now the fur­thest along. At the same con­fer­ence, J&J un­veiled a batch of ear­li­er stage da­ta. It was small­er — 29 pa­tients — but every pa­tient re­spond­ed by month 6. Both ther­a­pies tar­get BC­MA, or B-cell mat­u­ra­tion agent, a pro­tein ex­pressed al­most ex­clu­sive­ly on ma­lig­nant cells.

The ther­a­py, though, comes with the same po­tent side ef­fects as pre­vi­ous CAR-T treat­ments. Cy­tokine re­lease syn­drome, the po­ten­tial­ly dead­ly side ef­fect in which ac­ti­vat­ed white blood cells send the im­mune sys­tem in­to in­flam­ma­to­ry over­drive, oc­curred in 83% of pa­tients in the ide-cel tri­al. How­ev­er, on­ly 5.5% were clas­si­fied as “se­vere.”

Liso-cel and ide-cel would be the third and fourth CAR-T treat­ments ap­proved since No­var­tis’s Kym­ri­ah and Gilead/Kite Phar­ma’s Yescar­ta and were ap­proved in 2017, al­though a sec­ond CAR–T ther­a­py from Kite Phar­ma al­so cur­rent­ly sits be­fore the FDA.

Af­ter the ASH da­ta, an­a­lysts ex­pect both BMS CAR-Ts to clear the fin­ish line, al­though Syed raised ques­tions about whether, amid Covid-19, the com­pa­ny’s cell ther­a­py man­u­fac­tur­ing fa­cil­i­ty in Wash­ing­ton state had been and would be able to be FDA-in­spect­ed. But not­ing that liso-cel al­ready was sub­mit­ted in De­cem­ber and giv­en pri­or­i­ty re­view in Feb­ru­ary, he gave a 90% chance of ide-cel ap­proval and wrote that “we would ar­gue there is a de­cent chance here the plant has al­ready been in­spect­ed and the con­cerns may be overblown.”

How long the ther­a­py re­mains a top op­tion for mul­ti­ple myelo­ma pa­tients is a dif­fer­ent ques­tion. At ASH, BMS al­so showed da­ta for CC-93269, a BC­MA-tar­get­ing bis­pe­cif­ic an­ti­body that put up “crazy num­bers,” as Baird an­a­lyst Bri­an Sko­r­ney put it: 89% ORR, 33% CR. Re­gen­eron al­so showed off its BC­MA bis­pe­cif­ic. Safer and dra­mat­i­cal­ly sim­pler to ad­min­is­ter, these an­ti­bod­ies may ul­ti­mate­ly win out, Sko­r­ney said.

”We think the true com­mer­cial op­por­tu­ni­ty is re­al­ized by the most safe­ly com­bin­able as­set with gener­ic Revlim­id/Vel­cade,” he wrote. “As such, al­though fur­ther be­hind than BC­MA-CART, we see these drugs leap­ing ahead in the treat­ment par­a­digm, bar­ring ma­jor safe­ty is­sues.”

Inside FDA HQ (File photo)

The FDA just ap­proved the third Duchenne MD drug. And reg­u­la­tors still don’t know if any of them work

Last year Sarepta hit center stage with the FDA’s controversial reversal of its CRL for the company’s second Duchenne muscular dystrophy drug — after the biotech was ambushed by agency insiders ready to reject a second pitch based on the same disease biomarker used for the first approval for eteplirsen, without actual data on the efficacy of the drug.

On Wednesday the FDA approved the third Duchenne MD drug, based on the same biomarker. And regulators were ready to act yet again despite the lack of efficacy data.

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Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

Franz-Werner Haas, CureVac CEO

UP­DAT­ED: On the heels of a snap $1B raise, Cure­Vac out­lines plans to seek emer­gency OK for their Covid-19 vac­cine in a mat­ter of months

CureVac is going from being one of the quietest players in the race to develop a new vaccine to fight the worst public health crisis in a century to a challenger for the multibillion-dollar market that awaits the first vaccines to make it over the finish line. Typically low-key at a time of brash comments and incredibly ambitious development timelines from the leaders, CureVac now is jumping straight into the spotlight.

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US gov­ern­ment re­port­ed­ly be­gins prepar­ing for Covid-19 chal­lenge tri­als. Are they eth­i­cal?

Controversial human challenge trials for potential Covid-19 vaccines reportedly have a new booster — the US government.

Scientists working for the government have begun manufacturing a strain of the novel coronavirus that could be used in such studies, Reuters reported Friday morning. The trials would enroll healthy volunteers to be vaccinated and then intentionally infected with a weakened coronavirus.

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Trevor Martin (Mammoth)

Eye­ing in-vi­vo edit­ing, Mam­moth li­cens­es Jen­nifer Doud­na’s new CRISPR en­zyme

Last month, Jennifer Doudna revealed in Science a new, “hyper-compact” CRISPR enzyme that was half the size of traditional CRISPR enzymes and could, she suspected, offer a new, more versatile tool for gene editing.

Now, the University of California-Berkeley has licensed that enzyme, known as Casφ, exclusively to a biotech startup she and two former students set up three years ago: Mammoth Biosciences. It’s the second new CRISPR protein Mammoth has licensed from Doudna’s lab, after they licensed Cas14 in 2019.

Sanofi vet Kather­ine Bowdish named CEO of PIC Ther­a­peu­tics; As the world Terns: Liv­er dis­ease biotech makes ex­ec­u­tive changes

PIC Therapeutics hasn’t raised much money, yet. But the fledgling biotech has attracted a high-profile player to the helm.

The Boston-based biotech has handed the reins to Katherine Bowdish as its president and CEO. Bowdish will also join the board of directors of PIC. Bowdish joins from Sanofi where she served as VP and head of R&D strategy, as well as helping launch and lead Sanofi Sunrise, a venture investment and partnering vehicle at Sanofi. Before that, Bowdish held several exec roles at Permeon Biologics, Anaphore, Alexion Pharmaceuticals and Prolifaron (acquired by Alexion).

Clockwise from left: Canaccord Genuity principal Michelle Gilson, Canaccord Genuity CSO Brian Mueller and BioMarin CSO Hank Fuchs (Canaccord Genuity webcast)

Bio­Marin CSO diss­es ri­vals for the he­mo­phil­ia A gene ther­a­py crown: Way be­hind, fac­ing big re­cruit­ment chal­lenges and at best a .6 on the gen-one scale

The leader in the race to a hemophilia A gene therapy does not like to be compared unfavorably to the competition. And when their top execs do the comparing, don’t look for any modesty — BioMarin, they say, owns the lead.

As Factor VIII expression wanes over time, quite a few analysts have raised questions about the kind of future BioMarin’s gene therapy — a supposed once-and-done treatment — faces if it stops working. But just 7 days away from their PDUFA date, with high odds of success, the top execs clearly feel that they are way out front, while promising their rivals will discover there’s a tough slog ahead trying to pursue trials where large numbers of patients are ineligible for new therapies.

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Cal­lid­i­tas bets up to $102M on a biotech buy­out, snag­ging a once-failed PBC drug

After spending years developing its oral formulation of the corticosteroid budesonide, Sweden’s Calliditas now has its sights set on the primary biliary cholangitis field.

The company will buy out France-based Genkyotex, and it’s willing to bet up to €87 million ($102 million) that Genkyotex’s failed Phase II drug, GKT831, will do better in late-stage trials.

Under the current agreement, Calliditas $CALT will initially pay €20.3 million in cash for 62.7% of Genkyotex (or €2.80 a piece for 7,236,515 shares) in early October, then circle back for the rest of Genkyotex’s shares under the same terms. If nothing changes, the whole buyout will cost Calliditas €32.3 million, plus up to  €55 million in contingent rights.

James Wilson, WuXi Global Forum at JPM20

FDA puts up a red light for Pas­sage Bio’s first gene ther­a­py pro­gram, de­lay­ing a pro­gram from James Wilson's group at Penn

Gene therapy pioneer James Wilson spearheaded animal studies demonstrating the potential of new treatments injected directly into the brain, looking to jumpstart a once-and-done fix for an extraordinarily rare disease called GM1 gangliosidosis in infants. His team at the University of Pennsylvania published their work on monkeys and handed it over to Passage Bio, a Wilson-inspired startup building a pipeline of gene therapies — with an IND for PBGM01 to lead the way.

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