Mer­ck cau­tious­ly steps in­to the PD-(L)1/CT­LA-4 check­point fray. But should it ‘go big or go home’ in­stead?

Mer­ck’s strat­e­gy on de­vel­op­ing its PD-1 check­point drug Keytru­da could be sum­ma­rized as: If we have any kind of a shot at a le­git­i­mate tar­get, we’re go­ing to take it. Then we’ll start a com­bo tri­al AS­AP.

Now it’s moved in­to an ear­ly-stage study in what is loom­ing as the next big chal­lenge that will ei­ther dis­tin­guish the lead­ers or set up the next great pit­fall: A PD-(L)1/CT­LA-4 com­bo.

Tim An­der­son

The think­ing be­hind this, out­lined in a note from Bern­stein’s Tim An­der­son, helps il­lus­trate just how in­tense­ly com­pet­i­tive this game of block­busters has be­come, pit­ting Mer­ck $MRK against Bris­tol-My­ers Squibb $BMY (again) and a very am­bi­tious group at As­traZeneca $AZN that has been mak­ing some close­ly-watched in­roads in the field this year.

Mer­ck’s lat­est ear­ly-stage com­bo match­es its in-house CT­LA-4 drug MK-1308 with Keytru­da, its check­point star that has moved in­to a dom­i­nant po­si­tion in the fast-chang­ing field.

Roger Perl­mut­ter, Mer­ck

“(T)here is a dif­fer­en­ti­a­tion that we’re hop­ing for. And it is a mol­e­cule that was ob­tained in part ex­ter­nal­ly and re­fined in­ter­nal­ly,” Mer­ck R&D chief Roger Perl­mut­ter told An­der­son. “We’ve been work­ing on it for some time.”

As An­der­son ob­serves, there is on­ly one CT­LA-4 drug on the mar­ket. That is Bris­tol-My­ers Yer­voy, which is in a com­bi­na­tion study al­ready. As­traZeneca, though, is com­ing up fast with a com­bi­na­tion of Imfinzi and its CT­LA-4 treme­li­mum­ab in their MYS­TIC study, which will ei­ther help them vault ahead or il­lus­trate why there has been grow­ing skep­ti­cism about the com­bo. Yer­voy and CT­LA-4 drugs in gen­er­al have been linked with con­sid­er­able tox­i­c­i­ty, and more re­cent re­ports un­der­score some strong doubts about its fu­ture in check­point com­bos.

Perl­mut­ter ad­mit­ted as much to An­der­son, who thinks that Mer­ck would be bet­ter off shoot­ing for a com­bi­na­tion study with Yer­voy now rather than wait­ing for the ex­per­i­men­tal in-house drug to come along. An­der­son writes:

We have felt that if MRK is go­ing to pur­sue CT­LA4 com­bo – ei­ther as a hedge, or be­cause it gen­uine­ly be­lieves in the op­por­tu­ni­ty – it ei­ther needs to “go big or go home.”  As a com­pound just en­ter­ing first-in-hu­man stud­ies, MK-1308 is far be­hind BMY and AZN.  Un­less MRK be­lieves it has a dif­fer­en­ti­at­ed prod­uct, it is dif­fi­cult to jus­ti­fy de­vel­op­ment of this new mol­e­cule giv­en the sub­stan­tial lead-time ad­van­tage that its two com­peti­tors have in this area.

How­ev­er, MRK’s pur­suit of MK-1308 be­comes eas­i­er to jus­ti­fy if MRK were to si­mul­ta­ne­ous­ly get its feet wet more quick­ly by a com­bi­na­tion study of Keytru­da+Yer­voy (even if on­ly a short­er, quick­er, “prac­tice-en­abling” study, sim­i­lar to what BMY’s CM-568 was sup­posed to be).  This way, Keytru­da would re­main rel­e­vant in the near­er-term in a CT­LA4 com­bi­na­tion set­ting should tri­als like MYS­TIC (AZN) or Check­mate-227 (BMY) show fa­vor­able re­sults.  As long as MRK gen­er­ates clin­i­cal da­ta like this, physi­cians would like­ly feel com­fort­able mix­ing-and-match­ing MRK’s and BMY’s sep­a­rate prod­ucts.  Then, MRK has more time to even­tu­al­ly come in with a CT­LA4 of its own.

We’ll find out lat­er this year and next how these check­point com­bos line up against the check­point/chemo com­bi­na­tions that have been mov­ing in­to prac­tice. But An­der­son al­so notes that there is a swelling wave of fol­low-up tri­als to watch with IDO and more com­bi­na­tions mov­ing in­to Phase III.

In­di­vid­ual com­bi­na­tion strate­gies have to evolve. Just don’t look for any of the big play­ers, or the sec­ond-gen com­peti­tors lin­ing up, to slow down now.

Here comes the oral GLP-1 drug for di­a­betes — but No­vo Nordisk is­n't dis­clos­ing Ry­bel­sus price just yet

Novo Nordisk’s priority review voucher on oral semaglutide has paid off. The FDA approval for the GLP-1 drug hit late Friday morning, around six months after the NDA filing.

Rybelsus will be the first GLP-1 pill to enter the type 2 diabetes market — a compelling offering that analysts have pegged as a blockbuster drug with sales estimates ranging from $2 billion to $5 billion.

Ozempic, the once-weekly injectable formulation of semaglutide, brought in around $552 million (DKK 3.75 billion) in the first half of 2019.

As Nas­daq en­rolls the fi­nal batch of 2019 IPOs, how have the num­bers com­pared to past years?

IGM Biosciences’ upsized IPO haul, coming after SpringWorks’ sizable public debut, has revved up some momentum for the last rush of biotech IPOs in 2019.

With 39 new listings on the books and roughly two more months to go before winding down, Nasdaq’s head of healthcare listings Jordan Saxe sees the exchange marking 50 to 60 biopharma IPOs for the year.

“December 15 is usually the last possible day that companies will price,” he said, as companies get ready for business talks at the annual JP Morgan Healthcare Conference in January.

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A fa­vorite in Alex­ion’s C-suite is leav­ing, and some mighty sur­prised an­a­lysts aren’t the least bit hap­py about it

Analysts hate to lose a biotech CFO they’ve come to trust and admire — especially if they’re being blindsided by a surprise exit.

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Oxitec biologist releases genetically modified mosquitoes in Piracicaba, Brazil in 2016 [credit: Getty Images]

In­trex­on unit push­es back against claims its GM mos­qui­toes are mak­ing dis­ease-friend­ly mu­tants

When the hysteria of Zika transmission sprang into the American zeitgeist a few years ago, UK-based Oxitec was already field-testing its male Aedes aegypti mosquito, crafted to possess a gene engineered to obliterate its progeny long before maturation.

But when a group of independent scientists evaluated the impact of the release of these genetically-modified mosquitoes in a trial conducted by Oxitec in Brazil between 2013 and 2015, they found that some of the offspring had managed to survive — prompting them to speculate what impact the survivors could have on disease transmission and/or insecticide resistance.

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Pur­due threat­ens to walk away from set­tle­ment, asks to pay em­ploy­ees mil­lions in bonus­es

There are two updates on the lawsuit against Purdue Pharma over its role in fueling the opioid epidemic, as the Sackler family threatens to walk away from their pledge to pay out $3 billion if a bankruptcy judge does not stop outstanding state lawsuits against them. At the same time, the company has asked permission to pay millions in bonuses to select employees.

Purdue filed for chapter 11 bankruptcy this week as part of its signed resolution to over 2,000 lawsuits. The deal would see the Sackler family that owns Purdue give $3 billion from their personal wealth and the company turned into a trust committed to curbing and reversing overdoses.

Aerial view of Genentech's campus in South San Francisco [Credit: Getty]

Genen­tech sub­mits a big plan to ex­pand its South San Fran­cis­co foot­print

The sign is still there, a quaint reminder of whitewashed concrete not 5 miles from Genentech’s sprawling, chrome-and-glass campus: South Francisco The Industrial City. 

The city keeps the old sign, first erected in 1923, as a tourist site and a kind of civic memento to the days it packed meat, milled lumber and burned enough steel to earn the moniker “Smokestack of the Peninsula.” But the real indication of where you are and how much has changed both in San Francisco and in the global economy since a couple researchers and investors rented out an empty warehouse 40 years ago comes in a far smaller blue sign, resembling a Rotary Club post, off the highway: South San Francisco, The Birthplace of Biotech.

While No­var­tis ban­ish­es Zol­gens­ma scan­dal scars — Bio­gen goes on a Spin­raza 'of­fen­sive'

While Novartis painstakingly works to mop up the stench of the data manipulation scandal associated with its expensive gene therapy for spinal muscular atrophy (SMA) Zolgensma— rival Biogen is attempting to expand the use of its SMA therapy, Spinraza. 

The US drugmaker $BIIB secured US approval for Spinraza for use in the often fatal genetic disease in 2016. The approval covered a broad range of patients with infantile-onset (most likely to develop Type 1) SMA. 

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Eye­ing big ther­a­peu­tic push, Gink­go bags $290M to build a cell pro­gram­ming em­pire

Ginkgo Bioworks is on a roll. Days after publicizing a plan to nurture new startups via partnerships with accelerators Y Combinator and Petri, the Boston biotech says it has raised another $290 million for its cell programming platform to reach further and wider.

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UP­DAT­ED: Speak­er Nan­cy Pelosi to un­veil bill for fed­er­al­ly ne­go­ti­at­ed drug prices

After months of buzz from both sides of the aisle, Speaker Nancy Pelosi will today introduce her plan to allow the federal government to negotiate prices for 250 prescription drugs, setting up a showdown with a pharmaceutical industry working overtime to prevent it.

The need to limit drug prices is a rare point of agreement between President Trump and Democrats, although the president has yet to comment on the proposal and will likely face pressure to back a more conservative option or no bill at all. Republican Senator Chuck Grassley is reportedly lobbying his fellow party members on a more modest proposal he negotiated with Democratic Senator Ron Wyden in July.