The res­ur­rec­tion of LUM001: Mike Grey gets his drug back from Shire — along with $120M to gam­ble on PhI­II tri­als

EX­CLU­SIVE: In drug de­vel­op­ment, fail­ure isn’t al­ways fa­tal. Just ask Mike Grey.

When Grey com­plet­ed his deal to sell Lu­me­na to Shire back in 2014 for $260 mil­lion-plus, Shire was left in full con­trol of the charge to what it hoped would be a near-term ap­proval for a drug de­signed to con­trol ex­cess bile acids and ex­treme itch­ing.

A year lat­er, though, the lead pro­gram for LUM001 was ap­par­ent­ly in tat­ters, with an ug­ly mid-stage fail­ure for rare cas­es of Alag­ille syn­drome (AL­GS) that ap­peared to wipe out the block­buster val­ue Shire CEO Flem­ming Orn­skov had once en­vi­sioned when he did the deal. Then 2 years ago there was an­oth­er crit­i­cal tri­al break­down for the drug, then known as SHP625, with no sig­nif­i­cant re­duc­tion from base­line in serum al­ka­line phos­phatase or oth­er liv­er pa­ra­me­ters in pa­tients with pri­ma­ry scle­ros­ing cholan­gi­tis (PSC).

But it wasn’t dead. 

Alex Doren­baum

To­day, 4 years af­ter he ced­ed con­trol of the oral in­hibitor of the api­cal sodi­um de­pen­dent bile acid trans­porter, Grey is step­ping up with a fresh batch of top-line da­ta that has helped res­ur­rect the failed ther­a­py, along with a $120 mil­lion mega-round to launch the new com­pa­ny he’s put to­geth­er to make that hap­pen. And Shire — now soon to be merged with Take­da — has hand­ed over the world­wide rights to the drug for an un­spec­i­fied up­front and eq­ui­ty in the start­up.

“Clear­ly the tri­als did not turn out as you hoped,” Grey tells me in a phone in­ter­view from Lon­don as he wrapped the new con­tract. “Some­times, it takes a lit­tle time to get it right.”

Su­san Dubé

LUM001/SHP625 is now dubbed mar­al­ix­i­bat, which Grey says had a suc­cess­ful per­for­mance in Shire’s Phase IIb study called ICON­IC in AL­GS. An im­proved tri­al de­sign helped pave the way to a suc­cess­ful in­ter­im read­out at 48 weeks with sig­nif­i­cant re­duc­tions in bile acids and pru­ri­tus com­pared to place­bo. He al­so ob­tained pos­i­tive re­sults from a sub­group analy­sis in PF­IC, land­ing the right kind of da­ta to gain a break­through drug des­ig­na­tion from the FDA.

Armed with the new mon­ey from a group of deep pock­et­ed in­vestors — who are al­so en­dors­ing the da­ta and the drug and Mike Grey — Mirum is prep­ping a pair of Phase III stud­ies slat­ed to be­gin as ear­ly as pos­si­ble in 2019. 

Grey is go­ing for it, and he has the mon­ey need­ed to get it done and on to the FDA. Af­ter that, he’s plan­ning to be ready to launch mar­ket­ing op­er­a­tions — though he isn’t rul­ing out a buy­out along the way.

Cia­ra Kennedy

How much did he pay to get the drug back, along with rights to an­oth­er drug called volix­i­bat, the oth­er AS­BT in­hibitor from Lu­me­na once known as LUM002?

“Some­what less than what it sold for,” is all he’s say­ing this week.

It’s un­like­ly that any­one knows more about this drug than Grey, who nev­er gave up on it. Get­ting a drug back from a buy­er isn’t easy un­der any cir­cum­stances. But these deals have re­al po­ten­tial. Just ask John Hood, who got his drug fe­dra­tinib back from Sanofi years af­ter a land­mark col­lapse and then al­most im­me­di­ate­ly flipped it to Cel­gene for $1.1 bil­lion in cash — plus bil­lions more in mile­stones — at the be­gin­ning of this year.

Grey’s al­so not alone. Al­so buy­ing in to the res­ur­rec­tion of LUM001 is his lean-and-mean crew of 10 drawn from the old Lu­me­na team along with some se­lect To­bi­ra vets, in­clud­ing:

  • Chris Peetz has been ap­point­ed as pres­i­dent of Mirum and a mem­ber of the com­pa­ny’s board of di­rec­tors
  • Pamela Vig joins as chief sci­en­tif­ic of­fi­cer
  • Lara Long­pre will serve as the com­pa­ny’s chief de­vel­op­ment of­fi­cer
  • Shelly Xiong has been ap­point­ed head of reg­u­la­to­ry
  • Co-founders and ad­vis­ers: Alex Doren­baum, Su­san Dubé, Cia­ra Kennedy and Niall O’Don­nell.
Niall O’Don­nell

New En­ter­prise As­so­ci­ates led the round with par­tic­i­pa­tion from Deer­field Man­age­ment, Fra­zier Health­care Part­ners, No­vo Hold­ings A/S, Pap­pas Cap­i­tal, River­Vest Ven­ture Part­ners and Rock Springs Cap­i­tal. And they’re pro­vid­ing the board to watch things play out: Ed Math­ers, part­ner, NEA; Patrick Heron, man­ag­ing gen­er­al part­ner, Fra­zier Health­care Part­ners; Jonathan Leff, part­ner, Deer­field; Ti­ba Aynechi, part­ner, No­vo Hold­ings; and Niall O’Don­nell, man­ag­ing di­rec­tor, River­Vest.

They’re all suit­ed up, and ready to tack­le late-stage tri­als.

Im­age: Mike Grey. PAP­PAS CAP­I­TAL

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.