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.

Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen scores a pri­or­i­ty re­view for its Alzheimer's drug ad­u­canum­ab, mov­ing one gi­ant leap for­ward in its con­tro­ver­sial quest

Biogen scored a big win at the FDA today as regulators accepted their application for the controversial Alzheimer’s drug aducanumab and gave it a priority review.

The PDUFA date is March 7, 2021.

Significantly, Biogen says it did not use its priority review voucher to win special treatment at the FDA. The agency handed that out gratis.

That’s the ideal scenario Biogen was looking for as disappointed analysts wondered aloud about the delayed application earlier in the year.

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Ryan Watts, Denali CEO

Bio­gen hands De­nali $1B-plus in cash, $1B-plus in mile­stones to part­ner on late-stage Parkin­son’s drug

Biogen is handing over more than a billion dollars cash to partner with the up-and-coming neurosciences crew at Denali on a new therapy for Parkinson’s. And the big biotech is ready to pile on more than a billion dollars more in milestones — if the alliance is a success.

For Biogen $BIIB, the move on Denali’s small molecule inhibitors of LRRK2 puts them in line to collaborate on a late-stage program for DNL151, which is scheduled to start next year.

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Per­cep­tive fields SPAC #3 as an­oth­er group of biotechs scoops up $364M in lat­est Nas­daq romp

There’s no sign that the windfall of cash dropping biotech’s way on Wall Street is abating. Three more biopharmas priced IPOs on Thursday and Friday morning, riding a historic boom with a $364 million payoff.

London-based biotech Freeline Therapeutics took home the lion’s share of the cash with $159 million after pricing 8,823,529 shares at $18 a pop. Checkmate Pharmaceuticals, of Cambridge, MA, raised $75 million with an offer of 5 million shares at $15 — right at the midpoint of its range. And Arya Sciences Acquisition Corp III, the third in a series from Perceptive, priced 13,000,000 shares at $10 per share.

Bio­haven adds near­ly $1B in Nurtec deals with Roy­al­ty Phar­ma, Sixth Street

Biohaven just added nearly $1 billion to their balance sheet.

On Friday morning, the neuroscience biotech announced a pair of creative agreements with Royalty Pharma and the investment firm Sixth Street to bolster the commercial launch of their new migraine drug, Nurtec. Biohaven will sell a sliver of its royalties on Nurtec and 3% of the royalties on their experimental migraine drug zavegepant to Royalty Pharma as part of a larger agreeement that will pay $450 million. At the same time, the company announced they took out a $500 million loan from Sixth Street.

Ab­b­Vie set­tles in­sur­ance fraud suit, agrees to tweak nurse am­bas­sador pro­gram; CStone aims for NSCLC OK with pos­i­tive PhI­II da­ta

AbbVie has resolved a California lawsuit alleging insurance fraud in the promotion of its cash cow Humira, paying $24 million to settle things with the state’s insurance regulator.

The settlement comes almost four years after a whistleblower first reported AbbVie’s practice of deploying registered nurses to visit patients at home or call them by phone to ensure that Humira prescriptions are filled. AbbVie was also charged with providing illegal kickbacks to doctors in an attempt to encourage them to prescribe Humira for a range of anti-inflammatory diseases.

Covid-19 roundup: Gates Foun­da­tion pours $150M in­to In­dia’s Serum In­sti­tute; Pfiz­er teams with Gilead on remde­sivir

By CEO and scion Adar Poonawalla’s estimation, the Serum Institute in India has already poured hundreds of millions of dollars into scaling up the unproven Covid-19 vaccine being developed by AstraZeneca and Oxford for use in low and middle income countries. It’s meant taking on a risk that other companies, including AstraZeneca, have mitigated with huge amounts of government funding.

Now, for the first time, Poonawalla is getting some outside help. The Gates Foundation has agreed to pay the institute $150 million to supply 100 million vaccines to India and other emerging economies next year, Reuters reported. That includes both the vaccine being developed by AstraZeneca and the one being developed by Novavax. Those vaccines will be available in 92 countries and be priced at $3 per dose.

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In sur­pris­ing set­back, com­bo of Roche’s Tecen­triq and chemo fails to help pa­tients with triple-neg­a­tive breast can­cer

Roche broke ground last year when they secured the first FDA approval for a checkpoint therapy in triple-negative breast cancer, a notoriously difficult-to-treat indication that has been passed over by the wave of targeted therapies.

Now, though, doctors are puzzling over why a combination of drugs meant to make that therapy more potent instead appeared to make it less effective.

Roche said Thursday that in a Phase III trial, combining their PD-1/L1 checkpoint therapy Tecentriq with the chemotherapy paclitaxel, did not significantly improve progression-free survival for patients with locally advanced or metastatic triple-negative breast cancer over giving those patients chemotherapy alone. In fact, patients on the Tecentriq-chemo arm had lower overall survival than patients on chemo, although the drugmaker cautioned that the trial was not powered for that endpoint and the data were immature.

Jan Hatzius (Photographer: Christopher Goodney/Bloomberg via Getty Images)

When will it end? Gold­man econ­o­mist gives late-stage vac­cines a good shot at tar­get­ing 'large shares' of the US by mid-2021 — but the down­side is daunt­ing

It took decades for hepatitis B research to deliver a slate of late-stage candidates capable of reining the disease in.

With Covid-19, the same timeline has devoured all of 5 months. And the outcome will influence the lives of billions of people and a multitrillion-dollar world economy.

Count the economists at Goldman Sachs as optimistic that at least one of these leading vaccines will stay on this furiously accelerated pace and get over the regulatory goal line before the end of this year, with a shot at several more near-term OKs. That in turn should lead to the production of billions of doses of vaccines that can create herd immunity in the US by the middle of next year, with Europe following a few months later.

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Yvonne Greenstreet, incoming Alnylam president (Alnylam)

Al­ny­lam pres­i­dent Bar­ry Greene leaves af­ter 17 years, hand­ing po­si­tion over to Yvonne Green­street as biotech looks to­ward prof­itabil­i­ty

After 17 years helping Alnylam steer control of buzzy but unproven science they promised could change medicine, president Barry Greene is leaving the RNAi biotech just as that technology is beginning to hit prime time.

Leaving to “pursue outside interests in the biopharmaceutical industry,” the longtime executive will hand over the reins on October 1 to current COO Yvonne Greenstreet. Greenstreet, a former Pfizer and GlaxoSmithKline executive, inherits the high-profile spot at a company that’s proven its tech can work in rare diseases but now faces the daunting task of turning a couple successes and a new mountain of cash into drugs that are broadly applicable and, crucially, profitable.

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