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.

As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

Mer­ck wins a third FDA nod for an­tibi­ot­ic; Mereo tack­les TIG­IT with $70M raise in hand;

Merck — one of the last big pharma bastions in the beleaguered field of antibiotic drug development — on Friday said the FDA had signed off on using its combination drug, Recarbrio, with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The drug could come handy for use in hospitalized patients who are afflicted with Covid-19, who carry a higher risk of contracting secondary bacterial infections. Once SARS-CoV-2, the virus behind Covid-19, infects the airways, it engages the immune system, giving other pathogens free rein to pillage and plunder as they please — the issue is particularly pertinent in patients on ventilators, which in any case are breeding grounds for infectious bacteria.

RA Cap­i­tal, Hill­house join $310M rush to back Ever­est's climb to com­mer­cial heights in Chi­na

Money has never been an issue for Everest Medicines. With an essentially open tab from their founders at C-Bridge Capital, the biotech has gone two and a half years racking up drug after drug, bringing in top exec after top exec, and issuing clinical update after update.

But now other investors want in — and they’re betting big.

Everest is closing its Series C at $310 million. The first $50 million comes from the Jiashan National Economic and Technological Development Zone; the remaining C-2 tranche was led by Janchor Partners, with RA Capital Management and Hillhouse Capital as co-leaders. Decheng Capital, GT Fund, Janus Henderson Investors, Rock Springs Capital, Octagon Investments all joined.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

UP­DAT­ED: White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.