As­traZeneca wants a do-over on MYS­TIC com­bo da­ta. But a change­up in fo­cus won’t end the death watch on this pair­ing

As­traZeneca CEO Pas­cal So­ri­ot’s de­ci­sion to bet big on a check­point R&D strat­e­gy that re­lied heav­i­ly on its in-house com­bo of PD-L1 and CT­LA-4 is start­ing to look like a block­buster los­er. And this week’s push­back on a sub­set of the da­ta re­lat­ed to high tu­mor mu­ta­tion bur­den will like­ly do very lit­tle to change the odds here.

Bioreg­num Opin­ion Col­umn by John Car­roll

Re­searchers for the phar­ma gi­ant $AZN turned up at the Eu­ro­pean So­ci­ety for Med­ical On­col­o­gy Im­muno-On­col­o­gy 2018 Con­gress in Gene­va this week with more stun­ning­ly poor da­ta for the com­bi­na­tion of Imfinzi and treme­li­mum­ab, which was out­per­formed by Imfinzi alone — though the monother­a­py al­so failed to stand out in ad­vanced cas­es of non-small cell lung can­cer.

We al­ready knew that the haz­ard ra­tio for the com­bi­na­tion was a poor 0.85, but Imfinzi’s 24-month over­all sur­vival rate was 38.3% com­pared to an em­bar­rass­ing 35.4% for the PD-L1 plus CT­LA-4 ap­proach.

From As­traZeneca:

Among pa­tients re­ceiv­ing Imfinzi, 40.4% of pa­tients ex­pe­ri­enced a grade 3 or 4 ad­verse event (AE) vs. 47.7% with the Imfinzi plus treme­li­mum­ab com­bi­na­tion and 46.0% with chemother­a­py. 5.4% of pa­tients dis­con­tin­ued Imfinzi due to treat­ment-re­lat­ed AEs vs. 13.2% with the com­bi­na­tion and 9.4% on chemother­a­py.

Chloé Thé­paut

The com­pa­ny’s re­search team, though, was hop­ing to pull a vic­to­ry out of the mouth of de­feat by point­ing to a much bet­ter per­for­mance among pa­tients iden­ti­fied with a high tu­mor mu­ta­tion bur­den — putting them on the ex­act same path that Bris­tol-My­ers Squibb has tried to em­ploy with Op­di­vo plus Yer­voy. In that group there was a 36% drop in risk of death, with a haz­ard ra­tion of 0.64.

That would have to be con­firmed in a new study, though, be­fore reg­u­la­tors would con­sid­er it for ap­proval — which may in turn spur an­oth­er fol­low-up to Bris­tol-My­ers with a change­up in an on­go­ing tri­al to bring that clos­er to re­al­i­ty.

Bris­tol-My­ers’ own ap­proach to carv­ing out mar­ket share among TMB pa­tients, though, has failed to im­press an­a­lysts as more da­ta came out. Cred­it Su­isse in par­tic­u­lar not­ed a sim­i­lar­i­ty in sur­vival ben­e­fit for the low and high TMB groups in Bris­tol-My­ers’ da­ta set, which bodes ill for their mar­ket prospects.

And all of this is play­ing out as Mer­ck con­tin­ues to rack up big gains us­ing a com­bi­na­tion of Keytru­da and chemo in lung can­cer, which in­creas­ing­ly gains strength as the right com­bo to turn to ini­tial­ly to im­prove per­for­mance.

CT­LA-4 al­ready has a bad rep­u­ta­tion for tox­i­c­i­ty and mar­gin­al OS im­prove­ments that’s made it a tar­get for oth­ers look­ing to do bet­ter. Even­tu­al­ly, Yer­voy is like­ly to go down in his­to­ry as the check­point that re­vealed where these ther­a­pies could go. It was a mas­sive­ly im­por­tant start­ing point in a sto­ry that has many chap­ters to come.

Mean­while, the tidal wave of check­points and com­bo tri­als is com­ing up on the hori­zon, with plen­ty of op­por­tu­ni­ties for some­one else to make their mark as As­traZeneca con­tin­ues to fo­cus on MYS­TIC and treme­li­mum­ab.

But that game may al­ready be over, es­pe­cial­ly af­ter an­oth­er read­out for the As­traZeneca com­bo just days ago un­der­scored its fail­ure in head and neck can­cer.

Ear­li­er this week, Chloé Thé­paut, se­nior on­col­o­gy an­a­lyst for Glob­al­Da­ta, put it like this:

Un­less da­ta in fur­ther in­di­ca­tions, such as that ex­pect­ed from the KESTREL tri­al, can demon­strate su­pe­ri­or­i­ty of Imfinzi + treme­li­mum­ab over the stan­dard-of-care, or show im­pres­sive ef­fi­ca­cy or promis­ing safe­ty ver­sus com­pet­ing com­bi­na­tions, it is un­like­ly that As­traZeneca will have a dif­fer­en­ti­a­tion point suf­fi­cient for the com­bi­na­tion to be tak­en up on­to the mar­ket.

It may not be time yet to pre­pare the eu­lo­gy on this one, but it’s al­ready on death watch.

Im­age: Pas­cal So­ri­ot. GET­TY IM­AGES

Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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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.

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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Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

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Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

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.

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.

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.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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