No­var­tis promis­es a speedy CAR-T pitch, boasts about its slate of block­busters-to-be

No­var­tis sent out a loud and clear mes­sage this morn­ing: De­spite fold­ing its stand­alone cell ther­a­py unit, the phar­ma gi­ant says it re­mains on track to de­liv­er an ap­pli­ca­tion for its CAR-T CTL-019 for pe­di­atric acute lym­phoblas­tic leukemia “in ear­ly 2017.” And an ap­pli­ca­tion for dif­fuse large B cell lym­phoma is due in the sec­ond half of next year, which could put it well be­hind ri­val Kite Phar­ma. At the same time, the phar­ma gi­ant — now un­der as­sault from gener­ic com­pe­ti­tion — boast­ed about a dozen late-stage pro­grams with block­buster po­ten­tial to earn more than a bil­lion dol­lars a year.

James Brad­ner, Pres­i­dent, No­var­tis In­sti­tutes for Bio­Med­ical Re­search (NI­BR)

The lat­est CAR-T up­date is on one of the slides on of­fer this morn­ing for the Q3 re­view, as No­var­tis looks to re­as­sure in­vestors that a re­cent de­ci­sion to in­te­grate the cell and gene ther­a­py unit in its re­search or­ga­ni­za­tion — elim­i­nat­ing about 120 po­si­tions — has not de­railed its de­vel­op­ment ef­fort on the CAR-T front, where T cells are reengi­neered to tar­get can­cer cells.

No­var­tis had ea­ger­ly high­light­ed the biotech-like agili­ty of its in­de­pen­dent unit when it was es­tab­lished. But ques­tions have been grow­ing about just how well the pipeline of cell ther­a­pies has been ad­vanc­ing, es­pe­cial­ly af­ter ex­ecs or­dered the unit to be dis­solved. That move was quick­ly fol­lowed by No­var­tis’ de­ci­sion to cull the ranks of its R&D op­er­a­tion as it con­cen­trat­ed ef­forts in a few key hubs, search­ing for cost sav­ings by stream­lin­ing the or­ga­ni­za­tion.

Kite wants to file the first ap­pli­ca­tion for a CAR-T ap­proval in DL­B­CL be­fore the end of this year, pro­vid­ed the FDA al­lows it. Crit­ics, though, have won­dered if de­clin­ing re­sponse rates and a de­mand for more ma­ture da­ta will slow or scut­tle Kite’s play. Kite CEO Arie Bellde­grun re­cent­ly told me that even if the FDA wants to wait to see 6-month re­sults, they’ll have that in Feb­ru­ary. And he’s con­fi­dent that Kite can gain the first-mover ad­van­tage in the field.

Juno Ther­a­peu­tics, mean­while, had to post­pone its plans for an ap­pli­ca­tion this year af­ter its CAR-T drugs killed 4 peo­ple in two dif­fer­ent stud­ies, forc­ing re­searchers to drop flu­dara­bine from the drug reg­i­men used to prep pa­tients to pre­vent a lethal­ly tox­ic re­ac­tion to the ther­a­py. Now lag­ging be­hind in third place, the one­time con­tender has had to ad­just its po­si­tion on the im­por­tance of be­ing in the lead. In a re­cent in­ter­view with the Econ­o­mist, Juno CEO Hans Bish­op said be­ing first isn’t im­por­tant.

Both Kite and Juno al­so know that these pi­o­neer CAR-T ther­a­pies are deeply flawed and will quick­ly be over­tak­en by new tech­nolo­gies that amp up ef­fi­ca­cy and damp down safe­ty threats. Even­tu­al­ly, they al­so are look­ing to ad­vance off-the-shelf ther­a­pies that can re­place the per­son­al­ized meds that re­ly on pa­tient’s T cells.

An­a­lysts will be look­ing for some signs to­day that No­var­tis will be able to per­form in the sec­ond and third waves to come, when its cut­ting edge treat­ment will start to dull in com­par­i­son. With cell ther­a­py leader Oz Azam and oth­ers from the old unit now leav­ing No­var­tis, that will take some con­vinc­ing on their part.

Here’s its hit list of block­buster con­tenders and the time­line for hus­tling them to reg­u­la­tors:

  • There’s the CDK4/6 breast can­cer drug LEE011 (ri­bo­ci­clib), which has wrapped Phase III.
  • BAF312 (sipon­i­mod) for sec­ondary pro­gres­sive mul­ti­ple scle­ro­sis has al­so com­plet­ed late-stage de­vel­op­ment.
  • Next up is Fo­vista, an ap­tamer an­ti-PDGF in-li­censed from Oph­thotech that will read out in the piv­otal tri­al for neo­vas­cu­lar AMD dur­ing this quar­ter.
  • AMG 334 (part­nered with Am­gen), a CGRP re­cep­tor ag­o­nist for mi­graine, al­so reads out this quar­ter.
  • RLX030 (sere­lax­in) is on track for an H1 2017 read­out for heart fail­ure, a big fo­cus at No­var­tis.
  • RTH258 (brolu­cizum­ab) for neo­vas­cu­lar AMD al­so reads out in H1.
  • ACZ885 (canakinum­ab, Ilarus) should see piv­otal da­ta for CV risk re­duc­tion next year.
  • Cosen­tyx (AIN457) is on track to read out in 2018 for non-ra­di­ograph­ic ax­i­al SpA.
  • QVM149 should wrap up in asth­ma in 2018.
  • En­tresto will read out in a new in­di­ca­tion — heart fail­ure with pre­served EF — in 2019.
  • QAW039  (fe­vip­iprant) com­pletes on asth­ma in 2019.
  • And OMB157 (ofa­tu­mum­ab) rounds out the 2019 pro­jec­tion for re­laps­ing mul­ti­ple scle­ro­sis.

 

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials, and could help shore up public trust in the agency and any eventual vaccine.

Vas Narasimhan (AP Images)

UP­DAT­ED: Still held down by clin­i­cal hold, No­var­tis' Zol­gens­ma falls fur­ther be­hind Bio­gen and Roche as FDA asks for a new piv­otal study

Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

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Scoop: ARCH’s Bob Nelsen is back­ing an mR­NA up­start that promis­es to up­end the en­tire man­u­fac­tur­ing side of the glob­al busi­ness

For the past 2 years, serial entrepreneur Igor Khandros relied on a small network of friends and close insiders to supply the first millions he needed to fund a secretive project to master a new approach to manufacturing mRNA therapies.

Right now, he says, he has a working “GMP-in-a-box” prototype for a new company he’s building — after launching 3 public companies — which plans to spread this contained, precise manufacturing tech around the world with a set of partners. He’s raised $60 million, recruited some prominent experts. And not coincidentally, he’s going semi-public with this just as a small group of pioneers appears to be on the threshold of ushering in the world’s first mRNA vaccines to fight a worldwide pandemic.

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Isaac Veinbergs, Libra CEO

With $29M in Se­ries A, Boehringer-backed Li­bra looks to tack­le neu­rode­gen­er­a­tion through cel­lu­lar clean­ing

Can the natural process by which cells clean out toxic proteins be harnessed to create potential treatments for neurodegenerative disorders?

That’s the question Libra Therapeutics will be trying to answer, as the new biotech officially launched Wednesday morning with $29 million in Series A financing. The company has three preclinical programs at the ready, with its lead candidate targeting ALS and frontotemporal dementia. But CEO Isaac Veinbergs said he hopes to develop therapies for a wide range of diseases, including Parkinson’s, Alzheimer’s and Huntington’s.

Patrick Enright, Longitude co-founder (Longitude)

As its biotechs hit the pan­dem­ic ex­it, Lon­gi­tude rais­es $585M for new neu­ro, can­cer, ag­ing and or­phan-fo­cused fund

The years have been kind to Longitude Capital. This year, too.

A 2006 spinout of Pequot Capital, its founders started their new firm just four years before the parent company would go under amid insider trading allegations. Their first life sciences fund raised $325 million amid the financial crisis, they added a second for $385 million and then in, 2016, a third for $525 million. In the last few months, the pandemic biotech IPO boom netted several high-value exits from those funds, as Checkmate, Vaxcyte, Inozyme and Poseida all went public.

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Gene Wang, Immetas co-founder and CEO (file photo)

Im­metas Ther­a­peu­tics nabs $11M Se­ries A to nar­row their bis­pe­cif­ic work tar­get­ing in­flam­ma­tion in age-re­lat­ed dis­eases

How does a biotech celebrate its two-year anniversary? For Immetas Therapeutics, it’s with an $11 million Series A round and a game plan to fight age-related disease.

Co-founders Gene Wang and David Sinclair came together years ago around the idea that inflammation is the ultimate process driving age-related illnesses, including cancer. The duo launched Immetas in 2018 and packed the staff with industry experts. Wang, who says he’s always had an entrepreneurial spirit, has held lead roles at Novartis, GSK, Bristol Myers Squibb and Merck. He’s worked on blockbuster drugs like Humira, Gardasil, Varubi and Zolinza. And now, he’s channeling that spirit as CEO.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.