Celtaxsys spins 'clin­i­cal­ly mean­ing­ful' da­ta on an­oth­er failed PhII cys­tic fi­bro­sis study

At first glance, you would think At­lanta-based Celtaxsys had plen­ty to be hap­py about in its re­lease about their Phase II study of an ex­per­i­men­tal drug for cys­tic fi­bro­sis called ace­bilu­s­tat. The an­ti-in­flam­ma­to­ry drug had pro­duced the first “clin­i­cal­ly mean­ing­ful” ev­i­dence of its po­ten­tial to re­duce pul­monary ex­ac­er­ba­tions in pa­tients.

That must be worth a cel­e­bra­tion, right?

But if you look at it close­ly, the da­ta — such as they are — leave a lot to be de­sired.

First, the study was a fail­ure. The pri­ma­ry ef­fi­ca­cy end­point in the 200-pa­tient study was a clas­sic mea­sure of FEV1 from base­line — forced ex­pi­ra­to­ry vol­ume in 1 sec­ond — as out­lined in clin­i­cal­tri­als.gov. If you dig in­to their state­ment, you’ll find there was no dif­fer­ence in lung func­tion be­tween the drug and the con­trol arm.

So what about those “clin­i­cal­ly mean­ing­ful” ben­e­fits for pa­tients on pul­monary ex­ac­er­ba­tions? 

The com­pa­ny said there was a “19% re­duc­tion in PEx and a 22% re­duced risk in pro­gress­ing to first PEx ver­sus place­bo.” And in sub­group analy­sis, some pa­tients did even bet­ter. The pul­monary ex­ac­er­ba­tion re­sults were based on a per pro­to­col ba­sis as op­posed to in­tent-to-treat. 

I asked a spokesper­son for the com­pa­ny what p-val­ues the com­pa­ny had nailed down for these sec­ondary end­points. She replied that da­ta were be­ing held back for a fu­ture con­fer­ence (at least the part that wasn’t in the re­lease), then not­ed that the sec­ondary end­points on pul­monary ex­ac­er­ba­tions were not pow­ered suf­fi­cient­ly to de­ter­mine sta­tis­ti­cal sig­nif­i­cance.

OK. I replied. But the com­pa­ny had those p-val­ues, right? So what were they and could it be trans­lat­ed to sig­nif­i­cance?

Here’s what I got:

The re­duc­tion in the rate of pul­monary ex­ac­er­ba­tions and in­creased time to first PEx re­port­ed are nu­mer­ic re­duc­tions for pa­tients treat­ed with ace­bilu­s­tat, not sta­tis­ti­cal­ly sig­nif­i­cant.

For con­text, the mag­ni­tude and con­sis­ten­cy of the ef­fects across our key, pre-spec­i­fied sub­groups (i.e. mild lung dis­ease, con­comi­tant CFTR mod­u­la­tor ther­a­py) has been char­ac­ter­ized by the CF Foun­da­tion, who have ex­pressed con­tin­ued sup­port of our P3 pro­gram, as clin­i­cal­ly mean­ing­ful.

So you have a failed study with no hard ev­i­dence of a clear drug ben­e­fit for pa­tients, now be­ing steered in­to Phase III. The Reuters re­port help­ful­ly not­ed that the com­pa­ny is look­ing to raise funds some­how, though com­pa­ny ex­ecs haven’t ex­act­ly de­ter­mined how.

There’s been con­sid­er­able at­ten­tion on cys­tic fi­bro­sis as Ver­tex con­tin­ues to dom­i­nate the space and move for­ward with promis­ing com­bo stud­ies. A host of ri­vals have ap­peared, in­clud­ing Gala­pa­gos, but no one has pro­vid­ed any re­cent da­ta to sup­port one of these oth­er con­tenders.

Celtaxsys didn’t change that pic­ture to­day, ei­ther.

Fangliang Zhang, AP Images

Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom

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.

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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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.

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.

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.