Cerulean crash­es af­ter lead nano drug flubs its sec­ond PhII can­cer study

Cerulean Phar­ma’s lead nan­otech can­cer drug has run in­to an­oth­er stone wall in the clin­ic. The Waltham, MA-based biotech $CERU says that CR­LX101 com­bined with Avastin flubbed a Phase II study, fail­ing to pro­vide ev­i­dence of an im­prove­ment in pro­gres­sion-free sur­vival when com­pared against stan­dard of care ther­a­pies for re­nal cell car­ci­no­ma.

Cerulean’s shares were slammed on the news, plung­ing 62% and wip­ing out the li­on’s share of its $75 mil­lion mar­ket cap.

The drug com­bo group ac­tu­al­ly per­formed worse than the con­trol arm, with in­ves­ti­ga­tors re­port­ing a 3.7 month me­di­an PFS for Cerulean’s drug com­pared with 3.9 months for stan­dard of care. The ob­jec­tive re­sponse rate was even worse: 5% for the CR­LX101 com­bi­na­tion against 14% for stan­dard of care.

This wasn’t the first fail­ure for Cerulean. The drug, which com­bines tiny amounts of the an­ti­cancer tox­in camp­tothecin with a poly­mer mol­e­cule in or­der to in­fil­trate leaky tu­mors, al­so failed a study for non-small cell lung can­cer in 2014 that raised se­ri­ous doubts about the tech­nol­o­gy.

The set­back marks the end of a the­o­ry that CR­LX101 could play a key role in can­cer cell sur­vival by in­hibit­ing hy­pox­ia-in­ducible fac­tor-1α (HIF-1α). The fo­cus now will shift en­tire­ly to in­hibit­ing topoi­so­merase 1 (topo 1), which is in­volved in cel­lu­lar repli­ca­tion. The biotech has sev­er­al oth­er on­go­ing stud­ies.

“We are con­vinced that CR­LX101 is an ac­tive drug,” CMO Adri­an Senderow­icz told an­a­lysts in a call Wednes­day af­ter­noon, ze­ro­ing in on ear­ly clin­i­cal ev­i­dence of monother­a­py ac­tiv­i­ty for pan­creas and col­orec­tal can­ncer.

The stock crunch comes at a bad time. The biotech re­port­ed that it had $47 mil­lion in its cof­fers at the end of Q2, giv­ing it enough cash to make it through Q2 2017. CFO Gregg Beloff told an­a­lysts the com­pa­ny has op­tions to ex­tend the run­way in­to Q3 of next year, while ex­ecs look to some in­ter­im cat­a­lysts with on­go­ing pro­grams to fu­el a new fundrais­ing ef­fort. Cerulean took out a loan from Her­cules in ear­ly 2015, which won’t ease any con­cerns among the an­a­lysts about its cash po­si­tion fol­low­ing a hard set­back like this.

The biotech en­list­ed MIT’s pro­lif­ic nan­otech ex­pert Bob Langer for its sci­en­tif­ic ad­vi­so­ry board. The IPO boom of the past few years took a few nan­otech com­pa­nies like Cerulean on­to Nas­daq. But at least one – Bind Ther­a­peu­tics, a Langer lab spin­out – foundered and was re­cent­ly bought out of a bank­rupt­cy auc­tion by Pfiz­er.

Michael Schmidt at Leerink is tak­ing a more skep­ti­cal view of Cerulean’s fu­ture now. His com­ment:

“CR­LX-101 is be­ing al­so stud­ied in plat­inum-re­sis­tant ovar­i­an can­cer; how­ev­er with mod­er­ate sin­gle agent ac­tiv­i­ty in this topo1-sen­si­tive can­cer, we think it’s dif­fi­cult to in­ter­pret the ear­ly stage sin­gle-arm com­bi­na­tion da­ta. CR­LX-101 gen­er­at­ed 16% re­spons­es in 19 plat­inum re­sis­tant pa­tients sin­gle agent, 17% ORR in com­bi­na­tion w/ Avastin in 18 pts, and 5/9 (56%) in com­bi­na­tion with week­ly pa­cli­tax­el. Based on our pri­or MEDA­Corp KOL checks, we think more than 20-30% ORR would be re­quired to be con­sid­ered dif­fer­en­ti­at­ed in this in­di­ca­tion. Longer term we are more op­ti­mistic on the on­go­ing com­bi­na­tion study with Lyn­parza giv­en the stronger pre­clin­i­cal ra­tio­nale, but we think it’s still too ear­ly to as­sign val­ue to this opp’ty.”

Christo­pher D. T. Guiffre, Cerulean Pres­i­dent & CEO

“We are dis­ap­point­ed with this out­come and will un­der­take a thor­ough analy­sis of the da­ta to un­der­stand why CR­LX101 plus Avastin un­der­per­formed com­pared to the re­sults we saw in an ear­li­er in­ves­ti­ga­tor-spon­sored tri­al,” said Christo­pher D. T. Guiffre, Pres­i­dent and Chief Ex­ec­u­tive Of­fi­cer of Cerulean, in a state­ment. “This out­come did not sup­port our hy­poth­e­sis that tar­get­ing hy­pox­ia in­ducible fac­tor (HIF) in com­bi­na­tion with VEGF in­hibitor in RCC, a HIF-over­ex­press­ing tu­mor type, would be ben­e­fi­cial, so we will not pur­sue HIF as a tar­get go­ing for­ward. We will con­tin­ue to fo­cus on the po­tent topoi­so­merase 1 in­hi­bi­tion of CR­LX101’s pay­load, camp­tothecin, in topoi­so­merase 1-sen­si­tive tu­mors. Our com­bi­na­tions with week­ly pa­cli­tax­el and LYN­PARZA (ola­parib) are ex­am­ples of on­go­ing tri­als that lever­age CR­LX101’s topoi­so­merase 1 in­hi­bi­tion in com­bi­na­tion with chemother­a­pies and DNA dam­age re­pair agents.”

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.
GSK has had one of the most moribund R&D groups in Big Pharma for years. They proved over and over again that they were very slow to fail, while often sticking with programs with limited commercial upside in an effort to find something that worked. An earlier attempt to prod some changes with “biotech-like” research groups executive dedicated to its pipeline assets was a bust.

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.

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.