Roche is bring­ing back gan­tenerum­ab from the dead, tak­ing an­oth­er stab at Alzheimer’s PhI­II

Mar­lies Spro­ll, Mor­phoSys

Alzheimer’s drugs are ex­pen­sive to test and un­like­ly to suc­ceed, but they are al­so hard to kill.

More than two years af­ter gan­tenerum­ab failed de­ci­sive­ly in treat­ing ear­ly-stage Alzheimer’s, Roche is map­ping out an at­tempt­ed come­back through a new, piv­otal Phase III pro­gram that puts them back in­to the late-stage pipeline with their sec­ond ther­a­py.

In­ves­ti­ga­tors stub­born­ly vowed back at an in­ter­na­tion­al Alzheimer’s con­fer­ence in 2015 that if you amped up the dosage of the amy­loid be­ta an­ti­body it would be pos­si­ble to track a re­al treat­ment ef­fect for Alzheimer’s, im­prov­ing cog­ni­tion and func­tion. And now Roche part­ner Mor­phoSys, which con­tributed its plat­form tech in dis­cov­er­ing the drug, says the phar­ma gi­ant is go­ing for it — again.

The Ger­man biotech says that its con­tacts at Roche are plan­ning to launch two Phase III stud­ies in mild to pro­dro­mal pa­tients some­time lat­er in the year, stick­ing to a group of pa­tients who are just be­gin­ning to demon­strate symp­toms of the mem­o­ry-wast­ing ail­ment.

Roche nev­er gave up on gan­tenerum­ab. Roche neu­ro­science de­vel­op­ment chief Paulo Fon­toura tells me they’ve been us­ing two ex­tend­ed stud­ies to see if they can safe­ly use a much, much high­er dose need­ed to have an im­pact on the dis­ease with­out stir­ring up dan­ger­ous lev­els of ARIA-E, or brain swelling.

“We want­ed to find out if 4- or 5-fold (high­er dos­es) would be suc­cess­ful,” Fon­toura tells me, while con­trol­ling any cas­es of ARIA-E. And all in­di­ca­tions,he adds, is that they are on the right track.

Noth­ing has worked in Alzheimer’s R&D over the last 14 years, and gan­tenerum­ab looked like it would join a list of the most promi­nent drugs in the field to wash out of a big Phase III. But re­searchers have al­so been em­bold­ened by bet­ter di­ag­nos­tics to se­lect pa­tients as well as by the ear­ly da­ta from Bio­gen’s ad­u­canum­ab pro­gram which has shown glim­mers of ef­fi­ca­cy. Eli Lil­ly on­ly re­cent­ly wrapped its last piv­otal shot at solanezum­ab, its third straight fail­ure.

Mer­ck has al­so con­tributed to the drum­beat of fail­ures, re­cent­ly con­ced­ing de­feat in the most ad­vanced study of a BACE drug that tried to move up­stream in the dis­ease process, pre­vent­ing the pro­duc­tion of tox­ic lev­els of amy­loid be­ta. And Lund­beck flopped with its three Phase III stud­ies of their 5-HT6 an­tag­o­nist idalopir­dine, leav­ing Ax­o­vant as the last com­pa­ny to test that symp­to­matic ap­proach in a piv­otal study.

Why the ded­i­ca­tion? There are no drugs that can mod­i­fy the pro­gres­sion of Alzheimer’s and a big de­mand for any new symp­to­matic ther­a­pies that can slow the im­pact of the dis­ease, leav­ing the field wide open for a block­buster in­tro­duc­tion. And with every set­back, re­searchers in­sist that the same drugs could work un­der dif­fer­ent cir­cum­stances.

Now Roche will soon have two piv­otal pro­grams for Alzheimer’s back in the clin­ic, with gan­tenerum­ab run­ning along­side crenezum­ab.

“This is great news for Mor­phoSys. We are de­light­ed by the strong com­mit­ment to gan­tenerum­ab as a po­ten­tial new ther­a­py for Alzheimer’s dis­ease”, com­ment­ed Mar­lies Spro­ll, the chief sci­en­tif­ic of­fi­cer of Mor­phoSys AG. “The Hu­CAL-de­rived an­ti­body gan­tenerum­ab has prop­er­ties that we be­lieve make it a promis­ing can­di­date to treat Alzheimer’s dis­ease, and we look for­ward to learn­ing more about these new Phase III tri­als.”

Vlad Coric (Biohaven)

In an­oth­er dis­ap­point­ment for in­vestors, FDA slaps down Bio­haven’s re­vised ver­sion of an old ALS drug

Biohaven is at risk of making a habit of disappointing its investors. 

Late Friday the biotech $BHVN reported that the FDA had rejected its application for riluzole, an old drug that they had made over into a sublingual formulation that dissolves under the tongue. According to Biohaven, the FDA had a problem with the active ingredient used in a bioequivalence study back in 2017, which they got from the Canadian drugmaker Apotex.

Norbert Bischofberger. Kronos

Backed by some of the biggest names in biotech, Nor­bert Bischof­berg­er gets his megaround for plat­form tech out of MIT

A little over a year ago when I reported on Norbert Bischofberger’s jump from the CSO job at giant Gilead to a tiny upstart called Kronos, I noted that with his connections in biotech finance, that $18 million launch round he was starting off with could just as easily have been $100 million or more.

With his first anniversary now behind him, Bischofberger has that mega-round in the bank.

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Chas­ing Roche's ag­ing block­buster fran­chise, Am­gen/Al­ler­gan roll out Avastin, Her­ceptin knock­offs at dis­count

Let the long battle for biosimilars in the cancer space begin.

Amgen has launched its Avastin and Herceptin copycats — licensed from the predecessors of Allergan — almost two years after the FDA had stamped its approval on Mvasi (bevacizumab-awwb) and three months after the Kanjinti OK (trastuzumab-anns). While the biotech had been fielding biosimilars in Europe, this marks their first foray in the US — and the first oncology biosimilars in the country.

Seer adds ex-FDA chief Mark Mc­Clel­lan to the board; Her­cules Cap­i­tal makes it of­fi­cial for new CEO Scott Bluestein

→ On the same day it announced a $17.5 million Series C, life sciences and health data company Seer unveiled that it had lured former FDA commissioner and ex-CMS administrator Mark McClellan on to its board. “Mark’s deep understanding of the health care ecosystem and visionary insights on policy reform will be crucial in informing our thinking as we work to bring our liquid biopsy and life sciences products to market,” said Seer chief and founder Omid Farokhzad in a statement.

Daniel O'Day

No­var­tis hands off 3 pre­clin­i­cal pro­grams to the an­tivi­ral R&D mas­ters at Gilead

Gilead CEO Daniel O’Day’s new task hunting up a CSO for the company isn’t stopping the industry’s dominant antiviral player from doing pipeline deals.

The big biotech today snapped up 3 preclinical antiviral programs from pharma giant Novartis, with drugs promising to treat human rhinovirus, influenza and herpes viruses. We don’t know what the upfront is, but the back end has $291 million in milestones baked in.

Vas Narasimhan, AP Images

On a hot streak, No­var­tis ex­ecs run the odds on their two most im­por­tant PhI­II read­outs. Which is 0.01% more like­ly to suc­ceed?

Novartis CEO Vas Narasimhan is living in the sweet spot right now.

The numbers are running a bit better than expected, the pipeline — which he assembled as development chief — is performing and the stock popped more than 4% on Thursday as the executive team ran through their assessment of Q2 performance.

Year-to-date the stock is up 28%, so the investors will be beaming. Anyone looking for chinks in their armor — and there are plenty giving it a shot — right now focus on payer acceptance of their $2.1 million gene therapy Zolgensma, where it’s early days. And CAR-T continues to underperform, but Novartis doesn’t appear to be suffering from it.

So what could go wrong?

Actually, not much. But Tim Anderson at Wolfe pressed Narasimhan and his development chief John Tsai to pick which of two looming Phase III readouts with blockbuster implication had the better odds of success.

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Francesco De Rubertis

Medicxi is rolling out its biggest fund ever to back Eu­rope's top 'sci­en­tists with strange ideas'

Francesco De Rubertis built Medicxi to be the kind of biotech venture player he would have liked to have known back when he was a full time scientist.

“When I was a scientist 20 years ago I would have loved Medicxi,’ the co-founder tells me. It’s the kind of place run by and for investigators, what the Medicxi partner calls “scientists with strange ideas — a platform for the drug hunter and scientific entrepreneur. That’s what I wanted when I was a scientist.”

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Af­ter a decade, Vi­iV CSO John Pot­tage says it's time to step down — and he's hand­ing the job to long­time col­league Kim Smith

ViiV Healthcare has always been something unique in the global drug industry.

Owned by GlaxoSmithKline and Pfizer — with GSK in the lead as majority owner — it was created 10 years ago in a time of deep turmoil for the field as something independent of the pharma giants, but with access to lots of infrastructural support on demand. While R&D at the mother ship inside GSK was souring, a razor-focused ViiV provided a rare bright spot, challenging Gilead on a lucrative front in delivering new combinations that require fewer therapies with a more easily tolerated regimen.

They kept a massive number of people alive who would otherwise have been facing a death sentence. And they made money.

And throughout, John Pottage has been the chief scientific and chief medical officer.

Until now.

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H1 analy­sis: The high-stakes ta­ble in the biotech deals casi­no is pay­ing out some record-set­ting win­nings

For years the big trend among dealmakers at the major players has been centered on ratcheting down upfront payments in favor of bigger milestones. Better known as biobucks for some. But with the top 15 companies competing for the kind of “transformative” pacts that can whip up some excitement on Wall Street, with some big biotechs like Regeneron now weighing in as well, cash is king at the high stakes table.

We asked Chris Dokomajilar, the head of DealForma, to crunch the numbers for us, looking over the top 20 deals for the past decade and breaking it all down into the top alliances already created in 2019. Gilead has clearly tipped the scales in terms of the coin of the bio-realm, with its record-setting $5 billion upfront to tie up to Galapagos’ entire pipeline.

Dokomajilar notes:

We’re going to need a ‘three comma club’ for the deals with over $1 billion in total upfront cash and equity. The $100 million-plus club is getting crowded at 164 deals in the last decade with new deals being added towards the top of the chart. 2019 already has 14 deals with at least $100 million in upfront cash and equity for a total year-to-date of over $9 billion. That beats last year’s $8 billion and sets a record.

Add upfronts and equity payments and you get $11.5 billion for the year, just shy of last year’s record-setting $11.8 billion.

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