Third Rock sinks $59M in­to Cas­ma's 're­cy­cling' tech, with neu­ro on the mind

It feels like launch sea­son, and Third Rock is on a roll. The ven­ture fund and start­up in­cu­ba­tor is un­veil­ing yet an­oth­er biotech — its third pub­lic launch in a num­ber of weeks. This one is step­ping out with a $58.5 mil­lion Se­ries A, and a locked and loaded staff of au­tophagy ex­perts.

Beth Levine

The com­pa­ny, called Cas­ma Ther­a­peu­tics, has qui­et­ly been work­ing on tech­nol­o­gy that it hopes will ar­rest — or even re­verse — the pro­gres­sion of both rare and broad ge­net­ic dis­eases, in­clud­ing the fail­ure-rid­den space of neu­rode­gen­er­a­tion.

To do this, Cam­bridge, MA-based Cas­ma is us­ing new strate­gies to boost the body’s abil­i­ty to break down ma­te­r­i­al it no longer needs, like mis­fold­ed pro­teins, in­vad­ing pathogens, or spare or­ganelles. Think of it as the cell’s re­cy­cling sys­tem. When this slaugh­ter and sal­vage process (called au­tophagy) isn’t work­ing — or when it’s over­whelmed by dis­ease — all sorts of things can go awry.

Cas­ma’s CEO Kei­th Dionne tells me the com­pa­ny is look­ing at us­ing small mol­e­cules to drug var­i­ous pro­teins in­volved in trig­ger­ing au­tophagy. The idea is to in­ter­vene at strate­gic points in the au­tophagy process to boost the re­cy­cling sys­tem. And they’ve got pre­clin­i­cal da­ta that sug­gest turn­ing the di­al up on au­tophagy could lead to treat­ments for a wide range of dis­ease, in­clud­ing lyso­so­mal stor­age dis­or­ders, liv­er and mus­cle dis­eases, in­flam­ma­to­ry dis­or­ders, and neu­rode­gen­er­a­tion.

An­drea Bal­labio

“In pre­clin­i­cal mod­els, we’re see­ing a ma­jor ef­fect in a num­ber of dis­eases,” Dionne said. “And it’s proven to be quite safe. If you ge­net­i­cal­ly in­duce au­tophagy in mice, they live health­i­er, longer lives — freer of dis­ease.”

Cas­ma al­ready has “4 to 5” pro­grams in the pipeline, Dionne said.

James Hur­ley

In­ter­est in this field has been warm­ing up since 2016, when the dis­cov­ery of key mech­a­nisms in au­tophagy earned the No­bel Prize for Phys­i­ol­o­gy or Med­i­cine. Since then, the sci­ence has moved rapid­ly. Many com­pa­nies are now pur­su­ing the idea of au­tophagy’s im­pact on dis­ease.

“There are a num­ber of drugs known to en­hance au­tophagy as a side ef­fect,” Dionne said. “The key thing we want to do is go af­ter the spe­cif­ic mech­a­nism, with­out a lot of oth­er side ef­fects.”

Her­bert “Skip” Vir­gin

Cas­ma’s sci­en­tif­ic founders cer­tain­ly have loads of com­bined ex­pe­ri­ence in au­tophagy. Among them is Beth Levine, di­rec­tor of the Cen­ter for Au­tophagy Re­search, who’s rec­og­nized as a world­wide ex­pert in au­tophagy for her dis­cov­ery of the mam­malian au­tophagy gene, BECN1, and oth­er com­po­nents of the au­tophagy path­way. Then there’s An­drea Bal­labio, a leader in the field of tran­scrip­tion­al reg­u­la­tion of lyso­so­mal bio­gen­e­sis and au­tophagy; James Hur­ley, who per­formed ground­break­ing stud­ies to de­ter­mine the struc­ture and ac­tiv­i­ty of au­tophagy core com­plex­es; and Her­bert “Skip” Vir­gin, who forged new ground in the un­der­stand­ing of au­tophagy’s role in in­flam­ma­tion and im­mu­ni­ty.

Dionne said the com­pa­ny’s Se­ries A should get them 2 to 3 years of run­way, giv­ing the com­pa­ny the chance to de­vel­op spe­cif­ic en­hancers of au­tophagy and val­i­date if they’re work­ing.

Im­age: Kei­th Dionne. Cas­ma

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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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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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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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.