Pro­teosta­sis shares zoom north as their cys­tic fi­bro­sis dou­blet caus­es a stir in small study -- trig­ger­ing an on­line brawl

Some­times it’s the small­est stud­ies that gain the biggest re­ac­tions from the in­vest­ment crowd that fol­lows biotech.

Case in point: Lit­tle Pro­teosta­sis Ther­a­peu­tics hit big-time pay dirt on Thurs­day, watch­ing its stock $PTI swoop up 448% on some in­trigu­ing ear­ly da­ta on a hand­ful of pa­tients suf­fer­ing from cys­tic fi­bro­sis.

Meenu Chhabra, CEO

Break­ing 21 pa­tients ho­mozy­gous for the F508del mu­ta­tion in­to var­i­ous dose groups for their CF dou­blet ther­a­py, re­searchers teased out some sig­nif­i­cant re­sults for the few peo­ple in the high dose co­hort that was evalu­able at the time of the Phase I cut­off for their read­out.

For the 300 mg ppFEV1 co­hort there was a sta­tis­ti­cal­ly sig­nif­i­cant in­crease from base­line to day 7 of 6.3%, which reg­is­tered as a 5.9% in­crease on day 14. Com­pared to a place­bo, the same PTI-801 300 mg/PTI-808 300 mg co­hort hit +8.3% and +6.6% at 7 and 14 days. They added that they al­so tracked a sta­tis­ti­cal­ly sig­nif­i­cant de­crease in sweat chlo­ride con­cen­tra­tion from base­line.

There’s an­oth­er 400 mg co­hort that’s be­ing tracked now, with a triplet to fol­low.

The kick­er is here:

“The cur­rent im­prove­ment in ppFEV1 for stan­dard of care dou­blets is on av­er­age 3%-4% in the F508del ho­mozy­gous pa­tient pop­u­la­tion,” said Dami­an Downey, a lec­tur­er in res­pi­ra­to­ry med­i­cine at Queen’s Uni­ver­si­ty Belfast.

The num­bers got a close re­view by an­a­lysts in the field. Leerink’s Joseph Schwartz not­ed Pro­teosta­sis’ mixed re­sults as an add-on for Orkam­bi, from Ver­tex. But, he added, “PTI’s own pro­pri­etary com­bo bodes well in our view for pre­lim­i­nary triplet da­ta ex­pect­ed this quar­ter.”

Baird’s Bri­an Sko­r­ney al­so gave the da­ta a thumbs up as an in­di­ca­tor of the po­ten­tial of the triple:

The com­bo of PTI-808 and PTI-801 showed ini­tial FEV1 re­sults that are com­pa­ra­ble to Ver­tex’s Orkam­bi and Symdeko in cys­tic fi­bro­sis pa­tients. Al­though we be­lieve this com­bo would have a dif­fi­cult de­vel­op­ment path­way, giv­en the avail­abil­i­ty of the Ver­tex dou­blets, we do be­lieve it cre­ates an op­por­tu­ni­ty for it to de­vel­op its am­pli­fi­er, PTI-428, in a pro­pri­etary triple com­bi­na­tion. We will see ini­tial triple com­bo da­ta this quar­ter that we be­lieve will be a sig­nif­i­cant pos­i­tive cat­a­lyst for the stock.

Ver­tex stock dropped 3.5%, which trig­gered a de­fen­sive scrum on Twit­ter as some of the com­pa­ny’s de­fend­ers turned ug­ly on the pres­sure. So far, Ver­tex has stared down re­peat­ed chal­lenges to its fron­trun­ner sta­tus. But it didn’t get off so light­ly on this run.

Pro­teosta­sis’ KOLs, mean­while, will con­tin­ue to talk up their new-found sta­tus in CF.

”Dou­blet com­bi­na­tions, the cur­rent stan­dard of care for many CF pa­tients, are the bench­mark for cur­rent treat­ment in cys­tic fi­bro­sis.  These da­ta are the first re­sults seen us­ing an en­tire­ly new CF dou­blet, com­pare fa­vor­ably to stan­dard of care, and demon­strate the po­ten­tial of next-gen­er­a­tion CFTR mod­u­la­tors to fur­ther im­prove out­comes in this dis­ease,” said Carsten Schwarz, head of the Adult Cys­tic Fi­bro­sis Cen­tre, Lung-Trans­plan­ta­tion Pro­gram, and En­doscopy Unit, De­part­ment of Pe­di­atric Pneu­mol­o­gy and Im­munol­o­gy, Char­ité, Berlin Uni­ver­si­ty Med­ical Cen­ter. “I look for­ward to re­sults from the fourth dos­ing co­hort and to un­der­stand­ing the po­ten­tial of an­oth­er nov­el com­bi­na­tion, PTI-801, PTI-808 and PTI-428.”

Re­searchers will be adding more da­ta this quar­ter and in ear­ly 2019.

The fight­ing has just be­gun.

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.