New Lis­te­ria fears spot­light­ed as Aduro’s CRS-207 is slapped with par­tial hold

Aduro CEO Stephen Isaacs

Nag­ging fears that Aduro Biotech’s can­cer vac­cine CRS-207 could trig­ger se­ri­ous Lis­te­ria in­fec­tions mush­roomed in­to a se­vere set­back on Mon­day morn­ing as the biotech re­port­ed that it had to halt en­roll­ment in all of its clin­i­cal stud­ies us­ing that tech­nol­o­gy. The par­tial hold was in­sti­tut­ed by the FDA af­ter a pa­tient test­ed pos­i­tive for Lis­te­ria, which is sus­pect­ed to be CRS-207, Aduro’s lead can­cer vac­cine.

CRS-207 is made up of reengi­neered Lis­te­ria mono­cy­to­genes — re­mov­ing genes in or­der to dis­arm the bac­te­ria — that ex­press mesothe­lin, spark­ing an im­mune re­sponse to a pro­tein con­cen­trat­ed on can­cer cells. Aduro has matched it with an­oth­er can­cer vac­cine, GVAX, hop­ing to pro­vide a one-two punch against can­cer, with an op­tion to add on ad­di­tion­al drugs to con­tin­ue to build an at­tack on can­cer cells.

Aduro’s shares $ADRO were ham­mered ear­li­er this year by the fail­ure of a com­bo study for pan­cre­at­ic can­cer. And the stock dropped 12% in pre-mar­ket trad­ing on Mon­day.

This isn’t the first time that Aduro has had to deal with Lis­te­ria fears. Last fall its stock briefly tum­bled when a pa­tient tak­ing the ther­a­py — which is sup­posed to be reengi­neered to pre­vent in­fec­tions — de­vel­oped Lis­te­ria. That news was dis­closed in a SEC fil­ing, trig­ger­ing fears that a hold could be on the way for Aduro. This sec­ond case rais­es fresh con­cerns that the drug may not have been com­plete­ly dis­armed, as promised.

The new set­back came as a sur­prise to a num­ber of an­a­lysts, who had ex­pect­ed that Aduro would be re­port­ing re­sults from a triple com­bo study of CRS-207, GVAX and Bris­tol-My­ers Squibb’s Op­di­vo for pan­cre­at­ic can­cer. That tri­al and oth­ers which are ful­ly en­rolled will con­tin­ue on sched­ule. Tri­als that have been de­layed in­clude a Phase I ovar­i­an can­cer study as well as a glioblas­toma tri­al.

In a call with an­a­lysts, CEO Stephen Isaacs heav­i­ly em­pha­sized that this is a par­tial hold af­ter the sec­ond Lis­te­ria case seen in 350 treat­ed pa­tients. R&D chief Dirk Brock­st­edt added that the com­pa­ny be­lieves that it’s “like­ly” that the strain dis­cov­ered in the fe­male pa­tient is ‘207. And both em­pha­sized that they are prepar­ing to in­sti­tute changes to the tri­al, in­clud­ing a mod­i­fi­ca­tion of the tri­al pro­to­cols with a re­vi­sion in an­tibi­ot­ic treat­ment and their sur­veil­lance of the pa­tients af­ter treat­ment.

“We’re op­ti­mistic this is go­ing to be re­solved and we’re do­ing all we can to re­solve it,” Isaacs summed up.

Lis­te­ria was de­tect­ed on an “in­dwelling port” used on de­vices, and some an­a­lysts are spec­u­lat­ing that pa­tients with such ports are like­ly to be barred from treat­ment to re­duce the risk of in­fec­tion.

In their state­ment, Aduro re­port­ed:

Aduro is work­ing with the FDA to lift the par­tial hold so as to re­sume new pa­tient en­roll­ment in its LADD clin­i­cal tri­als. The com­pa­ny is re­vis­ing study pro­to­cols in ac­cor­dance with feed­back from the agency, in­clud­ing the mod­i­fi­ca­tion of an­tibi­ot­ic ad­min­is­tra­tion fol­low­ing treat­ment, ex­tend­ed pa­tient sur­veil­lance, and, as a pre-emp­tive mea­sure, ex­clu­sion of pa­tients who are on or will re­ceive cer­tain im­mune-sup­pres­sive treat­ments or who have cer­tain pros­thet­ic de­vices. Aduro will be pro­vid­ing pro­posed re­vi­sions to the pro­to­cols, pa­tient con­sent forms, and in­ves­ti­ga­tor brochures to the agency lat­er this week.

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

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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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.

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

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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.

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.

Samit Hirawat (Bristol Myers Squibb)

Af­ter bruis­ing re­jec­tion, blue­bird and Bris­tol My­ers Squibb land ide-cel pri­or­i­ty re­view. But will it mat­ter for the CVR?

With the clock all but up, the FDA accepted and handed priority review to Bristol Myers Squibb and bluebird bio’s BCMA CAR-T, keeping a narrow window open for Celgene investors to still cash in on the $9 CVR from the $63 billion Celgene merger.

The acceptance comes five months after the two companies weres slammed with a surprise refuse-to-file that threatened to foreclose the CVR entirely. Today’s acceptance sets the FDA decision date for March 27, 2021 – or precisely 4 days before the CVR deadline of March 31. Given the breakthrough designation and strong pivotal data — 81.5% response rate, 35.2% complete response rate — priority review was largely expected.

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