Fol­low­ing AS­CO pre­view flop, Syn­dax bets on new com­bo deal with Nek­tar

San Fran’s I/O dar­ling Nek­tar Ther­a­peu­tics $NK­TR is hand­ing off ac­cess to its pop­u­lar can­cer can­di­date NK­TR-214 to see how the ther­a­py fairs when paired with Syn­dax’s strug­gling drug enti­no­s­tat.

Brig­gs Mor­ri­son

The duo inked a col­lab­o­ra­tion and li­cens­ing deal that gives Syn­dax $SNDX the right to run a com­bo study test­ing the drugs against metasta­t­ic melanoma in pa­tients who have pre­vi­ous­ly pro­gressed when on an an­ti-PD-1.

The hope is that enti­no­s­tat, Syn­dax’s oral, small mol­e­cule Class 1 spe­cif­ic HDAC in­hibitor, could be put to good use along­side NK­TR-214, the CD122-bi­ased ag­o­nist that was the im­pe­tus be­hind Bris­tol-My­ers’ $3.6 bil­lion deal with Nek­tar back in Feb­ru­ary.

“Pre­vi­ous Phase II da­ta with enti­no­s­tat and high dose IL-2 in re­nal cell can­cer and our promis­ing pre­clin­i­cal da­ta gen­er­at­ed with NK­TR-214, laid the sci­en­tif­ic and clin­i­cal foun­da­tion for this col­lab­o­ra­tion,” said Brig­gs Mor­ri­son, CEO at Syn­dax, in a state­ment. “Work­ing with Nek­tar al­lows us to in­crease the po­ten­tial im­pact enti­no­s­tat may have in the treat­ment of PD-1 re­frac­to­ry metasta­t­ic melanoma pa­tients, and com­ple­ments the ex­cit­ing da­ta we have seen when com­bin­ing enti­no­s­tat with Keytru­da in a sim­i­lar pop­u­la­tion.”

Syn­dax needs this com­bo to work. That’s be­cause ear­li­er this month, the com­pa­ny shared an AS­CO ab­stract that sent Syn­dax’s stock plum­met­ing 23%. The com­pa­ny’s lead drug, enti­no­s­tat, large­ly flopped a mid-stage com­bo tri­al test­ing the drug with Keytru­da against NSCLC. The com­bo pro­duced an ob­jec­tive re­sponse rate of on­ly 11% in pre-treat­ed can­cer pa­tients — with a pro­gres­sion-free sur­vival rate of on­ly 2.5 months.

But Mor­ri­son and team found a sil­ver lin­ing: a post hoc analy­sis iden­ti­fied a sub­group of pa­tients who did bet­ter. Whit­tling the 57 pa­tients re­viewed for this read­out down to 14 with high mono­cyte lev­els, Syn­dax got a PFS rate of 5.4 months and an ORR of 29%.

Syn­dax will launch the Phase Ib tri­al in melanoma, with plans keep an eye on bio­mark­ers that might ID pa­tients with en­hanced re­spons­es, in­clud­ing “analy­ses ex­plor­ing the po­ten­tial of el­e­vat­ed lev­els of clas­si­cal pe­riph­er­al blood mono­cytes,” the com­pa­ny said.

“The com­bi­na­tion of NK­TR-214 and enti­no­s­tat demon­strat­ed a unique syn­er­gy in our pre­clin­i­cal mod­els which war­rants fur­ther study in the clin­ic,” said Jonathan Za­levsky, SVP and CSO of Nek­tar. “Im­por­tant­ly, we ob­served el­e­vat­ed lev­els of cy­tokine-pos­i­tive tu­mor-in­fil­trat­ing cy­to­tox­ic T cells fol­low­ing treat­ment with the com­bi­na­tion. We be­lieve this im­por­tant pre­clin­i­cal find­ing could trans­late to im­proved tu­mor re­spons­es in pa­tients who have be­come re­frac­to­ry to check­point in­hibitors. We look for­ward to work­ing with Syn­dax as this com­bi­na­tion ad­vances in­to the clin­ic.”

Fi­nan­cial de­tails of the deal weren’t dis­closed.

UP­DAT­ED: Clay Sie­gall’s $614M wa­ger on tu­ca­tinib pays off with solid­ly pos­i­tive piv­otal da­ta and a date with the FDA

Back at the beginning of 2018, Clay Siegall snagged a cancer drug called tucatinib with a $614 million cash deal to buy Cascadian. It paid off today with a solid set of mid-stage data for HER2 positive breast cancer that will in turn serve as the pivotal win Siegall needs to seek an accelerated approval in the push for a new triplet therapy.

And if all the cards keep falling in its favor, they’ll move from 1 drug on the market to 3 in 2020, which is shaping up as a landmark year as Seattle Genetics prepares for its 23rd anniversary on July 15.

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UP­DAT­ED: The FDA sets a reg­u­la­to­ry speed record, pro­vid­ing a snap OK for Ver­tex's break­through triplet for cys­tic fi­bro­sis

The FDA has approved Vertex’s new triplet for cystic fibrosis at a record-setting speed.

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IM­brave150: Roche’s reg­u­la­to­ry crew plans a glob­al roll­out of Tecen­triq com­bo for liv­er can­cer as PhI­II scores a hit

Just weeks after Bristol-Myers Squibb defended its failed pivotal study pitting Opdivo against Nexavar in liver cancer, Roche says it’s beat the frontline challenge with a combination of their PD-L1 Tecentriq with Avastin. And now they’re rolling their regulatory teams in the US, Europe and China in search of a new approval — badly needed to boost a trailing franchise effort.
Given their breakthrough and Big Pharma status as well as the use of two approved drugs, FDA approval may well prove to be something of a formality. And the Chinese have been clear that they want new drugs for liver cancer, where lethal disease rates are particularly high.
Researchers at their big biotech sub, Genentech, say that the combo beat Bayer’s Nexavar on both progression-free survival as well as overall survival — the first advance in this field in more than a decade. We won’t get the breakdown in months of life gained, but it’s a big win for Roche, which has lagged far, far behind Keytruda and Opdivo, the dominant PD-1s that have captured the bulk of the checkpoint market so far.
Researchers recruited hepatocellular carcinoma — the most common form of liver cancer — patients for the IMbrave150 study who weren’t eligible for surgery ahead of any systemic treatment of the disease.
Roche has a fairly low bar to beat, with modest survival benefit for Nexavar, approved for this indication 12 years ago. But they also plan to offer a combo therapy that could have significantly less toxicity, offering patients a much easier treatment regimen.
Cowen’s Steven Scala recently sized up the importance of IMbrave150, noting:

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That $335M JV Bay­er set up on CRISPR/Cas9? They’re let­ting the biotech part­ner car­ry on

Bayer committed $300 million to set up a joint venture on CRISPR/Cas9 tech with CRISPR Therapeutics $CRSP. But they’re handing off control now to the smaller biotech while retaining a couple of opt-ins for programs nearing an IND.

Bayer $BAY made much of the fact that they were going all-in on gene editing when they did their deal 3 years ago with CRISPR Therapeutics, which pitched $35 million in on their end. This was the cornerstone of their plan to set up new JVs that could make some serious leap forwards in hot new R&D spaces. Now CRISPR will have full management control of Casebia as they pursue programs in hemophilia, ophthalmology and autoimmune diseases.
Samarth Kulkarni, the CEO at CRISPR, made it sound like a natural progression.

J&J's block­buster Ste­lara wins US ap­proval for ul­cer­a­tive col­i­tis

J&J’s Stelara, which is set to be in the top ten list of blockbusters come 2025, is now cleared by the FDA for use in ulcerative colitis (UC), an inflammatory disease of the large intestine.

The biologic targets interleukin (IL)-12 and IL-23 cytokines, which are known to play a key role in inflammatory and immune responses. Stelara, which generated about $4.7 billion in the first nine months of 2019, is a key player in the crowded marketplace of drugs to treat autoimmune disorders such as psoriasis, rheumatoid arthritis and Crohn’s disease. AbbVie’s star therapy, Humira, continues to dominate, despite its looming patent cliff in the United States, while others including J&J’s $JNJ own anti-IL23 Tremfya, Lilly’s $LLY anti-IL-17 Taltz and AbbVie’s $ABBV recently approved anti-IL-23 antibody Skyrizi carve out a slice of market share.

Drug com­pa­nies reach $260M set­tle­ment just ahead of opi­oid tri­al; Oys­ter Point set terms for $85M IPO

→ Hours before the first federal opioid trial was set to begin, three drug distributors and an opioid manufacturer agreed to a $260 million agreement settlement, the Wall Street Journal was the first to report. The deal — which will see McKesson, Cardinal Health and AmerisourceBergen pay $215 million to Summit and Cuyahoga counties, and Teva deal out $35 million in cash and addiction treatments — does not resolve the pending, nationwide litigation that may result in a settlement worth upwards of $40 billion. Negotiators in that case, brought by 2,300 tribes, counties and cities nationwide and led by several states’ attorneys general, worked through much of Friday without success. Josh Stein, the attorney general for North Carolina, said they were trying to put together a $48 billion deal.

GSK of­floads two vac­cines in $1.1B deal as it works to re­vive the pipeline

GlaxoSmithKline is leaving the deep dark woods and its viruses behind.

GSK has agreed to divest its vaccines for rabies, RabAvert, and tick-born encephalitis vaccine, Encepur, to Bavarian Nordic, part of the company’s broader efforts to narrow its pipeline and focus on oncology and immunology.

The deal is worth up to nearly $1.1 billion, with a $336 million upfront payment. GSK acquired the vaccines from Novartis as part of an exchange for their late-stage oncology programs in 2015 under former chief Sir Andrew Witty.

Pfiz­er gets some en­cour­ag­ing PhI­II news on a fran­chise sav­ior, but is a dos­ing ad­van­tage worth the $295M up­front?

Close to 3 years after Opko tried to defend itself as shares tumbled on the news that its long-acting growth hormone had failed to outperform a placebo, the Pfizer partner $PFE is back. And this time they’re pitching Phase III data that demonstrate their drug is non-inferior — or maybe a tad better — than their well-known but fading standard in the field.
The comparator drug here is Genotropin, which earned a marginal $142 million for Pfizer last year — down 9% from the year before. Approved 24 years ago, biosimilars are now in development that Pfizer would like to stay out in front of. The market leader here is Norditropin, a growth hormone from Novo Nordisk that uses the same basic ingredient as Genotropin, which the Danish company sells with a kid-friendly self-injectable pen. That would also present some big competition if the new therapy from Opko/Pfizer makes it to the market.
The new data, says researchers, underscore that a weekly injection of somatrogon performed as well or slightly better than Genotropin (somatropin) in young children with growth hormone deficiency. Investigators tracked height velocity at 10.12 cm/year, edging out the older drug’s 9.78 cm/year. That 0.33 difference may not prove compelling to payers, though, who have been known to overlook dosing advantages in favor of lower costs.
That message may have weighed on the stock reaction this morning, with a 30%-plus hike $OPK giving way to more marginal gains.
Back in late 2016, Opko had to defend itself against a devastating Phase III setback as their initial late-stage trial failed against a sugar pill. Opko later blamed that setback on outliers in the study, though it wasn’t able to expunge the failure.

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As­traZeneca's Farx­i­ga scores FDA nod to cut risk of hos­pi­tal­iza­tion for heart fail­ure in di­a­bet­ics

While the FDA recently spurned an application to allow AstraZeneca’s blockbuster drug Farxiga for type 1 diabetes that cannot be controlled by insulin, citing safety concerns — the US regulator has endorsed the use of the SGLT2 treatment to reduce the risk of hospitalisation for heart failure in patients with type-2 diabetes and established cardiovascular disease or multiple CV risk factors.