Award-win­ning sep­sis project gets $13M and a shot at re­open­ing an R&D av­enue as FDA pitch­es out old gold stan­dard

As chair of the British Heart Foun­da­tion’s trans­la­tion­al awards com­mit­tee, David Grainger was pow­er­ful­ly at­tract­ed to some re­search that Glas­gow Uni­ver­si­ty pro­fes­sor James Leiper was do­ing on a com­mon symp­tom of sep­tic shock, a ma­jor killer that is re­spon­si­ble for more than a quar­ter mil­lion deaths in the US each year.

That was good for an award.

David Grainger

But now Grainger, a part­ner at Medicxi, has fol­lowed through with an $13 mil­lion ven­ture round to cre­ate a vir­tu­al com­pa­ny called Crit­i­cal Pres­sure that could take this as­set through ear­ly-stage stud­ies and in­to the hands of com­mer­cial buy­er.

And this time, it’s per­son­al.

Sep­sis is a se­vere, of­ten life threat­en­ing bac­te­r­i­al in­fec­tion that is fought off with an­tibi­otics. Dur­ing that fight the hu­man body can ex­pe­ri­ence tox­ic shock af­ter gen­er­at­ing ni­tric ox­ide, which dri­ves down blood pres­sure to a crit­i­cal point. For years now, doc­tors have fought back with no­ra­dren­a­line to con­strict blood ves­sel tis­sue and dri­ve the pres­sure back up, which can al­so be harm­ful.

So in re­search pri­mar­i­ly at Uni­ver­si­ty Col­lege Lon­don, Leiper de­vel­oped CPL001, a chem­i­cal com­pound that in­hibits an en­zyme called DDAH1.

James Leiper

“In­hibit­ing DDAH1 pre­vents the dra­mat­ic loss of blood pres­sure that of­ten ac­com­pa­nies sep­sis,” said the pro­fes­sor. “The body nat­u­ral­ly pro­duces a chem­i­cal, ni­tric ox­ide, that kills bac­te­ria but al­so low­ers blood pres­sure. Block­ing DDAH1 pre­vents the drop in blood pres­sure, with­out los­ing the abil­i­ty to fight the in­fec­tion.”

“It is try­ing to sta­bi­lize the pa­tient so that the at­tempts to deal with the un­der­ly­ing in­fec­tion have the time to be ef­fec­tive,” Grainger tells me. It’s some­thing he’s seen first hand, when his moth­er died from sep­sis sev­er­al years ago.

Even so, Grainger says that sep­sis as a fo­cus in R&D has been as qui­et as a grave­yard in biotech, al­most en­tire­ly be­cause of the high bar set by the FDA in gain­ing new ap­provals for the con­di­tion. Reg­u­la­tors have de­mand­ed a 28-day all cause mor­tal­i­ty ben­e­fit as the gold stan­dard for the last 25 years.

“The FDA has set the bar so high that no one has been able to achieve it,” he says. “It’s on­ly in the last 6 to 9 months that the FDA changed their po­si­tion.”

In pre-IND talks with the FDA, reg­u­la­tors — in writ­ing — backed off that stan­dard, in­stead turn­ing to a much more pli­ant no­ra­dren­a­line-spar­ing stan­dard for the piv­otal end­point.

The next step is straight­for­ward. Start­ing with healthy vol­un­teers but quick­ly loop­ing in some sep­sis pa­tients, Grainger has es­tab­lished a com­plete­ly vir­tu­al com­pa­ny which will take the drug through an ear­ly-stage pro­gram. In about two years, he says, the mon­ey in the start­up round will de­liv­er proof-of-prin­ci­ple da­ta that a com­mer­cial bio­phar­ma can use to see if this is some­thing that could be quick­ly shep­herd­ed in­to the mar­ket, per­haps af­ter a small piv­otal study to con­firm the ear­li­er find­ing.

Grainger isn’t known as a high roller in the de­vel­op­ment world. He and Medicxi are known for ruth­less­ly cut­ting costs to a bone, and there will be no full timers on board to spend mon­ey. He’s ex­ec­u­tive chair­man, the sin­gle-as­set com­pa­ny will be based un­der an um­brel­la group in Babra­ham in Cam­bridge, UK, and a part-time COO will man­age the day-to-day.

It’s not com­pli­cat­ed, he adds. This is some­thing that should be quick­ly ap­par­ent if it’s work­ing and safe to use.

Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology
ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development
CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

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Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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Hal Barron. GSK

GSK's Hal Bar­ron her­alds their sec­ond pos­i­tive piv­otal for cru­cial an­ti-BC­MA ther­a­py, point­ing to a push for quick OKs in a crowd­ed field

Hal Barron has his second positive round of Phase III data in hand for his anti-BCMA antibody drug conjugate belantamab mafodotin (GSK2857916). And GSK’s research chief says the data paves the way for their drive in search of an FDA approval for treating multiple myeloma.

It’s hard to overestimate the importance of this drug for GSK, a cornerstone of Barron’s campaign to make a dramatic impact on the oncology market and provide some long-lost excitement for the pharma giant’s pipeline. They’re putting this BCMA program at the front of that charge — looking to lead a host of rivals all aimed at the same target.

We don’t know what the data are yet, but DREAMM-2 falls on the heels of a promising set of data delivered 5 months ago for DREAMM-1. There investigators noted that complete responses among treatment-resistant patients rose to 15% in the extra year’s worth of data to look over, with a median progression-free survival rate of 12 months, up from 7.9 months reported earlier. The median duration of response was 14.3 months.

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UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

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Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

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Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll

As­traZeneca’s Imfinzi/treme com­bo strikes out — again — in lung can­cer. Is it time for last rites?

AstraZeneca bet big on the future of their PD-L1 Imfinzi combined with the experimental CTLA-4 drug tremelimumab. But once again it’s gone down to defeat in a major Phase III study — while adding damage to the theory involving targeting cancer with a high tumor mutational burden.

Early Wednesday the pharma giant announced that their NEPTUNE study had failed, with the combination unable to beat standard chemo at overall survival in high TMB cases of advanced non-small cell lung cancer. We won’t get hard data until later in the year, but the drumbeat of failures will call into question what — if any — future this combination can have left.

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Why would Am­gen want to buy Alex­ion? An­a­lysts call hot­ly ru­mored takeover un­like­ly, but seize the mo­ment

A rumor that Amgen is closing in on buyout deal for Alexion has sparked a guessing game on just what kind of M&A strategy Amgen is pursuing and how much Alexion is worth.

Mizuho analyst Salim Syed first lent credence to the report out of the Spanish news outlet Intereconomía, which said Amgen is bidding as much as $200 per share. While the source may be questionable, “the concept of this happening doesn’t sound too crazy to me,” he wrote.