Aslan turns fo­cus to bil­iary tract can­cer as lead drug flops in PhII gas­tric can­cer study

About a year af­ter se­cur­ing the full rights to de­vel­op and com­mer­cial­ize var­l­i­tinib from Ar­ray Bio­Phar­ma $AR­RY, Aslan Phar­ma $AL­SN said the drug failed to con­fer a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion in tu­mors of pa­tients with gas­tric can­cer in a mid-stage study.

Carl Firth

The Sin­ga­pore-based com­pa­ny — which is run by for­mer BD chief for As­traZeneca Carl Firth and went pub­lic in an un­der­whelm­ing IPO last May — has es­sen­tial­ly aban­doned test­ing the ex­per­i­men­tal drug in pa­tients with gas­tric can­cer and will con­cen­trate on stud­ies in bil­iary tract can­cer and oth­er in­di­ca­tions, it said on Mon­day.

Orig­i­nal­ly de­vel­oped by Ar­ray, the drug is al­so known as ASLAN001 and is an oral, small mol­e­cule that in­hibits the ac­tiv­i­ty of epi­der­mal growth fac­tor re­cep­tors HER1, HER2 and HER4 — which are mu­tat­ed or over­ex­pressed in many tu­mors and typ­i­cal­ly cause un­con­trolled growth. Its mech­a­nism of ac­tion is sim­i­lar to that of Roche’s can­cer drug Her­ceptin, which tar­gets HER2.

In the study, var­l­i­tinib was be­ing test­ed as a first-line treat­ment in pa­tients with gas­tric can­cer in ad­di­tion to a stan­dard chemother­a­py reg­i­men. Af­ter 12 weeks of treat­ment, pa­tients giv­en the drug + chemother­a­py ex­pe­ri­enced an av­er­age tu­mor shrink­age of 22%, while those on chemother­a­py alone saw their tu­mors shrink by 12.5% — how­ev­er that dif­fer­ence was not deemed sta­tis­ti­cal­ly sig­nif­i­cant. Aslan’s shares were down 24% be­fore the bell.

In terms of safe­ty, 73.1% of pa­tients on the ex­per­i­men­tal drug reg­i­men ex­pe­ri­enced a grade 3 or high­er ad­verse event, ver­sus 88.5% of pa­tients on chemother­a­py alone, Aslan said.

Ac­cord­ing to clin­i­cal­tri­, about 50 pa­tients were en­rolled in the study, which, if pos­i­tive, was de­signed to evolve in­to a Phase III tri­al eval­u­at­ing the drug in hun­dreds of pa­tients.

Oth­er than di­et, to­bac­co use, gen­der (male) and age (60-80), gas­tric or stom­ach can­cer is al­so linked to in­fec­tion with H. py­lori bac­te­ria. Over time it can lead to pre­can­cer­ous changes to the in­ner lin­ing of the stom­ach, ac­cord­ing to the Amer­i­can Can­cer So­ci­ety (ACS), which es­ti­mates the num­ber of new cas­es of stom­ach can­cer have de­creased about 1.5% each year over the last decade in the Unit­ed States, al­though in the late 1930s, stom­ach can­cer was the lead­ing cause of can­cer death in the re­gion. In oth­er parts of the world, stom­ach can­cer is much more com­mon, par­tic­u­lar­ly in less de­vel­oped coun­tries, the ACS added.

Mark McHale

“First-line gas­tric can­cer is a very chal­leng­ing in­di­ca­tion to treat and the ma­jor­i­ty of pa­tients present with ad­vanced dis­ease at ini­tial di­ag­no­sis,” Aslan’s COO Mark McHale said in a state­ment. “To date, no tar­get­ed ther­a­pies have been ap­proved to treat gas­tric can­cer with low HER-fam­i­ly ex­pres­sion. Whilst we are dis­ap­point­ed by the study find­ings, we are en­cour­aged by the pos­i­tive safe­ty da­ta and re­main con­fi­dent that var­l­i­tinib’s po­tent pan-HER in­hi­bi­tion has the po­ten­tial to yield ben­e­fits in bil­iary tract can­cer where HER fam­i­ly ex­pres­sion is known to be high.”

Da­ta from a first-line bil­iary tract can­cer study will be pre­sent­ed at a med­ical con­fer­ence lat­er this week, while top-line da­ta from a piv­otal study in sec­ond-line bil­iary tract can­cer are ex­pect­ed in the sec­ond half of 2019, the com­pa­ny said.

“While the var­l­i­tinib clin­i­cal da­ta gen­er­at­ed to date…have demon­strat­ed some ac­tiv­i­ty, we con­tin­ue to want to see more clin­i­cal and mech­a­nis­tic val­i­da­tion for var­l­i­tinib giv­en that bil­iary tract can­cer has his­tor­i­cal­ly been a dif­fi­cult space for drug de­vel­op­ment and the mech­a­nis­tic ad­van­tages of var­l­i­tinib be­ing a pan-HER in­hibitor re­main un­clear, giv­en the im­pli­ca­tions of tar­get­ing HER4 re­main poor­ly un­der­stood. Over­all, while we’re pos­i­tive on Aslan’s Asia fo­cused de­vel­op­ment strat­e­gy and the ex­pe­ri­ence of the man­age­ment team, we want to see more clin­i­cal and mech­a­nis­tic val­i­da­tion for var­l­i­tinib in a cat­a­lyst-rich 2019,” Leerink an­a­lysts wrote in a note.

In 2017, Aslan re­port­ed that var­l­i­tinib in­duced a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion in tu­mor size in pa­tients with breast can­cer in a Phase II tri­al, but the drug did not con­fer any im­prove­ments in pro­gres­sion-free sur­vival or over­all sur­vival.

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.

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→ 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.

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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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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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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

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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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On a glob­al romp, Boehringer BD team picks up its third R&D al­liance for Ju­ly — this time fo­cused on IPF with $50M up­front

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They’re handing over $50 million to get their hands on BBT-877, an ATX inhibitor from Korea’s Bridge Biotherapeutics that was on display at a science conference in Dallas recently. There’s not a whole lot of data to evaluate the prospects here.

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MacroGenics CEO Scott Koenig shrugged off the departure of Servier, which paid $20 million to kick off the alliance and $20 million to option flotetuzumab — putting a heavily back-ended $1 billion-plus in additional biobuck money on the table for the anti-CD123/CD3 bispecific and its companion therapies.