De­nali launch­es a clin­i­cal quest on Alzheimer’s drug, bank­ing $155M in Take­da cash and scor­ing mon­key da­ta on BACE

Af­ter all the set­backs and fail­ures we’ve seen in Alzheimer’s re­search over the past 15 years, can a start­up boast­ing bet­ter tech­nol­o­gy beat the ter­ri­ble odds against them and score with a new drug?

We’re at the ear­ly stages of get­ting an an­swer to that ques­tion.

De­nali $DNLI an­nounced to­day that it is now try­ing just that, launch­ing a Phase I clin­i­cal study of its Alzheimer’s drug DNL747, its small mol­e­cule in­hibitor for RIPK1. It’s al­so start­ed a sec­ond hu­man study of its LRRK2 in­hibitor for Parkin­son’s dis­ease, which is its lead in­di­ca­tion. And the South San Fran­cis­co biotech re­port­ed that it’s banked a $155 mil­lion up­front from Take­da’s bil­lion-dol­lar part­ner­ship while scor­ing pos­i­tive ear­ly re­sults from a study in­volv­ing mon­keys for BACE1 — a mech­a­nism in Alzheimer’s that re­cent­ly failed de­ci­sive­ly for Mer­ck in Phase III.

That pri­mate study is par­tic­u­lar­ly im­por­tant, as it helps val­i­date De­nali’s be­lief that its An­ti­body Trans­port Ve­hi­cle — or ATV — tech­nol­o­gy can get past the blood brain bar­ri­er and de­liv­er a ther­a­py in­to the brain — a hur­dle that has stymied de­vel­op­ers in the past.

Alzheimer’s has proven to be the hard­est tar­get in bio­phar­ma R&D, de­feat­ing every­thing thrown at it for well over a decade in piv­otal tri­als. Mer­ck’s re­cent fail­ure on BACE, elim­i­nat­ing pro­duc­tion of amy­loid be­ta in pa­tients, proved to their re­searchers that it wouldn’t work in mid-to-mod­er­ate pa­tients. And they’re in the process of eval­u­at­ing the num­bers for prodomal pa­tients, where verube­ce­s­tat al­so failed.

De­spite the litany of fail­ures, though, the ex-Genen­tech gang — led by CEO Ryan Watts — that runs De­nali have pieced to­geth­er one of the most close­ly-watched ef­forts in the field, start­ing over with ge­net­i­cal­ly de­fined pa­tient groups and us­ing new tech from com­pa­nies like F-star. And de­spite the skep­ti­cism over tar­gets and dis­ease mod­i­fi­ca­tion, the biotech has been able to store $467 mil­lion in cash by the end of De­cem­ber, build­ing a mar­ket cap close to $2 bil­lion — be­fore the Take­da pay­ment came through. And the glob­al phar­ma com­pa­ny is on the hook for an­oth­er $85 mil­lion in pre­clin­i­cal mile­stones.

Im­age: Ryan Watts. UNI­VER­SI­TY OF UTAH via YOUTUBE

Hal Barron, GSK

Break­ing the death spi­ral: Hal Bar­ron talks about trans­form­ing the mori­bund R&D cul­ture at GSK in a crit­i­cal year for the late-stage pipeline

Just ahead of GlaxoSmithKline’s Q2 update on Wednesday, science chief Hal Barron is making the rounds to talk up the pharma giant’s late-stage strategy as the top execs continue to woo back a deeply skeptical investor group while pushing through a whole new R&D culture.

And that’s not easy, Barron is quick to note. He told the Financial Times:

I think that culture, to some extent, is as hard, in fact even harder, than doing the science.

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Some Big Phar­mas stepped up their game on da­ta trans­paren­cy — but which flunked the test?

The nonprofit Bioethics International has come out with their latest scorecard on data transparency among the big biopharmas in the industry — flagging a few standouts while spotlighting some laggards who are continuing to underperform.

Now in its third year, the nonprofit created a new set of standards with Yale School of Medicine and Stanford Law School to evaluate the track record on trial registration, results reporting, publication and data-sharing practice.

Busy Gilead crew throws strug­gling biotech a life­line, with some cash up­front and hun­dreds of mil­lions in biobucks for HIV deal

Durect $DRRX got a badly needed shot in the arm Monday morning as Gilead’s busy BD team lined up access to its extended-release platform tech for HIV and hepatitis B.

Gilead, a leader in the HIV sector, is paying a modest $25 million in cash for the right to jump on the platform at Durect, which has been using its technology to come up with an extended-release version of bupivacaine. The FDA rejected that in 2014, but Durect has been working on a comeback.

In­tec blitzed by PhI­II flop as lead pro­gram fails to beat Mer­ck­'s stan­dard com­bo for Parkin­son’s

Intec Pharma’s $NTEC lead drug slammed into a brick wall Monday morning. The small-cap Israeli biotech reported that its lead program — coming off a platform designed to produce a safer, more effective oral drug for Parkinson’s — failed the Phase III at the primary endpoint.

Researchers at Intec, which has already seen its share price collapse over the past few months, says that its Accordion Pill-Carbidopa/Levodopa failed to prove superior to Sinemet in reducing daily ‘off’ time. 

Cel­gene racks up third Ote­zla ap­proval, heat­ing up talks about who Bris­tol-My­ers will sell to

Whoever is taking Otezla off Bristol-Myers Squibb’s hands will have one more revenue stream to boast.

The drug — a rising star in Celgene’s pipeline that generated global sales of $1.6 billion last year — is now OK’d to treat oral ulcers associated with Behçet’s disease, a common symptom for a rare inflammatory disorder. This marks the third FDA approval for the PDE4 inhibitor since 2014, when it was greenlighted for plaque psoriasis and psoriatic arthritis.

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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.

Apotex, though, has been a disaster ground. The manufacturer voluntarily yanked the ANDAs on 31 drugs — in late 2017 — after the FDA came across serious manufacturing deficiencies at their plants in India. A few days ago, the FDA made it official.

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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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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.