CymaBay scraps key NASH, PSC pro­grams af­ter lead drug trig­gers safe­ty alarms — share price im­plodes

When CymaBay Ther­a­peu­tics re­cent­ly ac­knowl­edged de­feat in a 12-week read­out of its Phase II tri­al of se­ladel­par, the biotech grasped at “sig­nif­i­cant im­prove­ments in bio­chem­i­cal mark­ers of liv­er in­jury” as a rea­son to re­main hope­ful about the 52-week biop­sy re­sults. But that hope is now dashed.

Not on­ly did the drug fail to re­duce liv­er fat, it al­so ap­peared to cause cell in­jury.

These “atyp­i­cal his­to­log­i­cal find­ings” — in­clud­ing cas­es of sus­pect­ed in­ter­face he­pati­tis — ob­served in pa­tients who re­spond­ed to their drug forced CymaBay to slam the brakes to its se­ladel­par clin­i­cal pro­gram, ter­mi­nat­ing the Phase IIb study in NASH in ques­tion and a Phase IIa in pri­ma­ry scle­ros­ing cholan­gi­tis (PSC) as well as putting all stud­ies in pri­ma­ry bil­iary cholan­gi­tis on hold.

“We are very dis­ap­point­ed in hav­ing to halt the de­vel­op­ment of se­ladel­par at this time but pa­tient safe­ty and care is para­mount,” CEO Su­jal Shah said in a state­ment.

Shares of the biotech $CBAY, which dipped in the wake of dis­ap­point­ing da­ta in June, are down a fur­ther 76.22% to $1.32 Mon­day morn­ing.

SVB Leerink an­a­lysts called it “a worst case sce­nario el­e­vat­ing safe­ty is­sues that are un­like­ly to be re­solved in the near fu­ture, in our opin­ion.”

“The risk/re­ward clear­ly fa­vors sig­nif­i­cant risk, even as we await ad­di­tion­al in­for­ma­tion and clar­i­ty from CBAY,” they wrote in a note. “Our mod­el is cur­rent­ly un­der re­view.”

But CymaBay’s good day turned out to be a good one for In­ter­cept, which has just clinched pri­or­i­ty re­view and a March 26, 2020 PDU­FA for their NASH drug obeti­cholic acid (OCA).

From Baird’s Bri­an Sko­r­ney:

This fol­lows a long his­to­ry of PPAR ag­o­nists blow­ing up (muragli­tazar, trogli­ta­zone) and high­lights what we be­lieve is an un­der­ap­pre­ci­a­tion of the risks of clin­i­cal de­vel­op­ment in the NASH space. OCA re­mains the on­ly med­ica­tion, to date, that has shown a fi­brot­ic ben­e­fit in a prospec­tive­ly de­fined con­trolled study, and its done it twice. We con­tin­ue to be­lieve OCA is like­ly to be the on­ly game in town for NASH for the fore­see­able fu­ture.

Safe­ty is­sues have pre­vi­ous­ly ben raised in the PPAR ag­o­nist class. This fam­i­ly of drugs ac­ti­vate pro­teins called per­ox­i­some pro­lif­er­a­tor-ac­ti­vat­ed re­cep­tors, which reg­u­late gene ex­pres­sion and are be­lieved to play a role in bile acid syn­the­sis, in­flam­ma­tion, fi­bro­sis and lipid me­tab­o­lism.

Back in 2007 Glax­o­SmithK­line aban­doned its own ef­fort in the field — a col­lab­o­ra­tion with Lig­and Phar­ma­ceu­ti­cals — af­ter their agent led to the for­ma­tion of tu­mors in an­i­mal tests. (The com­pound, GW501516, sub­se­quent­ly took on a sec­ond life as an il­le­gal per­for­mance-en­hanc­ing drug for ath­letes).

France’s Gen­fit and In­ven­ti­va are al­so work­ing on their own PPAR ag­o­nists for NASH. Gen­fit $GN­FT took a small­er toll on CymaBay’s ter­mi­na­tion news than it did fol­low­ing CymaBay’s ini­tial read­out, slid­ing 3.35% to $14.72. Al­most a year ago the drug­mak­er tout­ed that their elafi­bra­nor in­duced a sta­tis­ti­cal­ly sig­nif­i­cant de­crease in serum al­ka­line phos­phatase (ALP) lev­els for PBC pa­tients, and ear­li­er this year it won or­phan sta­tus for that in­di­ca­tion.

While the mar­ket ea­ger­ly awaits Phase III re­sults from Gen­fit, it has al­so se­cured a deal with Terns Phar­ma­ceu­ti­cals to bring the ther­a­py to Chi­na.

On CymaBay’s part, ex­ecs said they are in­ves­ti­gat­ing the sur­prise find­ings, which in­volved pa­tients who “demon­strat­ed on-study im­prove­ment or sta­bi­liza­tion of their bio­chem­i­cal mea­sures of in­flam­ma­tion and liv­er in­jury and no liv­er-re­lat­ed ad­verse events af­ter 52 weeks of treat­ment.”

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)

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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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)

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.

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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#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.