David Epstein, Evelo chairman (Flagship Pioneering)

Lit­tle Evelo sees big promise in its first cut of da­ta from a tiny study on atopic der­mati­tis

Any­one putting to­geth­er an ear­ly-stage tri­al in­volv­ing 24 pa­tients with a big-mar­ket dis­ease like atopic der­mati­tis wants to know one thing: Do they have a drug that’s ac­tive, with re­al po­ten­tial as a ther­a­py?

Evelo $EV­LO just posed that ques­tion, and the an­swer in the da­ta, says chair­man David Ep­stein, is yes.

“The drug starts to work at 2 weeks,” Ep­stein says as he looks at the da­ta. “That’s re­al­ly fast.”

In a mega-mar­ket field like se­vere eczema, the block­busters post piv­otal num­bers in­volv­ing big groups of pa­tients as they line up to take a shot at Dupix­ent. And it takes some awe­some re­sults to be com­pet­i­tive in a field of pow­er­ful bi­o­log­ics.

But lit­tle Evelo, with a mar­ket cap that’s like­ly be­low what those Phase II­Is cost, is com­pet­ing for a whole dif­fer­ent seg­ment. And this da­ta on 24 pa­tients, they be­lieve, of­fer ac­tu­al hu­man ev­i­dence that their mi­cro­bio­me strat­e­gy has a re­al chance of mak­ing it among a much larg­er num­ber of pa­tients with mild to mod­er­ate forms of AD as well as oth­er in­flam­ma­to­ry con­di­tions that are all linked to the same trig­gers.

The bot­tom line on the da­ta was sta­tis­ti­cal sig­nif­i­cance on 2 key scores in a place­bo com­par­i­son:

EASI (62% dif­fer­ence, p=0.034) and the per­cent­age change in IGA*BSA (71% dif­fer­ence, p=0.019)…At day 56, 10/16 pa­tients in the ac­tive group showed im­prove­ments in EASI score, with 4/16pa­tients hav­ing achieved an EASI50 clin­i­cal re­sponse, 3 of which achieved at least an EASI75, com­pared to 0/7 of­pa­tients in the place­bo group.

It was al­so proven tol­er­a­ble with no se­ri­ous ad­verse events.

All of that is crit­i­cal as the team at Evelo pur­sues mid-stage work on a drug that takes a page from na­ture and de­vel­ops a book of da­ta on this lead an­ti-in­flam­ma­to­ry treat­ment.

As Ep­stein ex­plains it, the mu­cos­al lin­ing of the stom­ach con­tains a hid­den mu­cos­al mi­cro­bio­me, and cer­tain bac­te­r­i­al strains can di­rect­ly speak to the im­mune sys­tem.

“We se­lect­ed our strains that in­crease or de­crease cy­tokines,” he says.

And in this in­stance you get an in­hibito­ry ef­fect on the TH2 in­flam­ma­to­ry re­sponse that dri­ves this dis­ease among cer­tain peo­ple.

So they de­vel­oped this drug that on­ly works in the gut, re­duc­ing the risk of any sys­temic safe­ty is­sues. The da­ta won’t work in se­vere cas­es, he adds, but the mild to mod­er­ate group rep­re­sent the li­on’s share of this mar­ket — and that’s just where they’re aimed.

This is sim­ply a pre­lim­i­nary in­di­ca­tion of ef­fi­ca­cy, a proof of con­cept study, of course. And the jour­ney ahead is long and high­ly risky. But the ev­i­dence that they could be on the right track was worth a 15% spike to the ad­mit­ted­ly beat­en-down val­ue of the shares.

So how do you pay to get a drug like this through a very ex­pen­sive piv­otal ef­fort?

Ep­stein, a Big Phar­ma vet with plen­ty of ex­pe­ri­ence on that side of the in­dus­try, says that “based up­on pre­vi­ous dis­cus­sions in the phar­ma in­dus­try, we’re quite cer­tain that phar­ma com­pa­nies will want to talk to us.”

The mi­cro­bio­me field over­all has had a mixed record on the in­vestor front, but Ep­stein al­so points out that Wall Street pays at­ten­tion when the da­ta are right, as Seres re­cent­ly demon­strat­ed.

Be­sides that, Evelo is a Flag­ship start­up, which rou­tine­ly en­joys rais­ing big sums for the plat­form com­pa­nies they back. And Ep­stein points to mul­ti­ple po­ten­tial read­outs in not just an­ti-in­flam­ma­to­ry ar­eas, but on­col­o­gy as well — where re­searchers are look­ing at how you can fight can­cer with their tech­nol­o­gy.

Evelo is pin­ning its hopes for big am­bi­tions on a small study. But at this im­por­tant mile­stone, Evelo be­lieves there’s good rea­son to think big.

UP­DAT­ED: Mer­ck pulls Keytru­da in SCLC af­ter ac­cel­er­at­ed nod. Is the FDA get­ting tough on drug­mak­ers that don't hit their marks?

In what could be an early shot in the battle against drugmakers that whiff on confirmatory studies to support accelerated approvals, the FDA ordered Bristol Myers Squibb late last year to give up Opdivo’s approval in SCLC. Now, Merck is next on the firing line — are we seeing the FDA buckling down on post-marketing offenders?

Merck has withdrawn its marketing approval for PD-(L)1 inhibitor Keytruda in metastatic small cell lung cancer as part of what it describes as an “industry-wide evaluation” by the FDA of drugs that do not meet the post-marketing checkpoints on which their accelerated nods were based, the company said Monday.

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Hal Barron, Endpoints UKBIO19

GSK, Vir's hopes for a Covid-19 an­ti­body fall flat in NIH 'mas­ter pro­to­col' with no ben­e­fit in hos­pi­tal­ized pa­tients

GlaxoSmithKline and Vir Biotechnology were hopeful that one of their partnered antibodies would carve out a win after getting the invite to a major NIH study in hospitalized Covid-19 patients. But just like Eli Lilly, the pair’s drug couldn’t hit the mark, and now they’ll be left to take a hard look at the game plan.

The NIH has shut down enrollment for GSK and Vir’s antibody VIR-7831 in its late-stage ACTIV-3 trial after the drug showed negligible effect in achieving sustained recovery in hospitalized Covid-19 patients, the partners said Wednesday.

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The 2021 top 100 bio­phar­ma in­vestors: As the pan­dem­ic hit and IPOs boomed, VCs swung in­to ac­tion like nev­er be­fore

The global pandemic may have roiled economies, killed hundreds of thousands and throttled entire industries, but the only effect it had on biopharma venture investing was to help turbocharge the field to giddy new heights.

Below you’ll find the new top 100 venture investors in the industry, ranked by the number of deals they were publicly involved in, as tracked by DealForma chief Chris Dokomajilar. The numbers master then calculated the estimated amount of money they put into each deal — divvying up the cash by the number of players — to indicate how they managed their syndicates.

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As Brain­Storm con­tin­ues to tout ‘clear sig­nal’ on ALS drug, the FDA of­fers a rare pub­lic slap­down on the da­ta

A little more than a week after BrainStorm acknowledged that regulators at the FDA had informed them that the biotech needed more data before it could expect to gain an approval for its ALS treatment NurOwn — while still touting a “clear signal” of efficacy and not ruling out an application — the agency has decided to clarify the record in a most unusual statement.

The FDA statement amounts to a straight slap own, offering a different set of efficacy numbers from the company’s public presentation last November and ruling out any chance of statistical significance.

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Eli Lil­ly claims suc­cess in a new JAK in­di­ca­tion: hair loss

Over the last decade, drugmakers have proven JAK inhibitors can treat a smattering of immune-related diseases ranging from rheumatoid arthritis to Covid-19. Now Eli Lilly has pulled out a new one.

Lilly and its biotech partner Incyte announced Wednesday that their JAK inhibitor baricitinib effectively regrew patients’ hair in a Phase III trial for alopecia areata, an autoimmune condition that can cause sudden, severe and patchy hair loss. Lilly didn’t break down the results from the 546-patient trial, but the primary endpoint was improvement on a standard score for alopecia symptoms.

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In­tro­duc­ing End­points FDA+, our new pre­mi­um week­ly reg­u­la­to­ry news re­port led by Zachary Bren­nan

CRLs. 483s. CBER, CDER and RWE. For biopharma professionals, these acronyms command attention because of the fundamental role FDA plays in drug development. Now Endpoints is doubling down on regulatory coverage, and launching a weekly report focusing on developments out of White Oak, with analysis and insight into what it all means.

Coverage will be led by our new senior editor, Zachary Brennan. He joins Endpoints from POLITICO, where he covered pharma. Prior to that he was the managing editor for Regulatory Focus, a news publication from the Regulatory Affairs Professionals Society.

Antoine Papiernik, Sofinnova managing director (Business Wire)

Sofinno­va Part­ners stays fo­cused on late-stage deals with a new, $540M crossover fund

One of Europe’s most high-profile biopharma investors is getting $540 million to invest in new crossover deals for late-stage companies.

The Paris-based VC says the fresh Sofinnova Crossover Fund raise positions them as the “largest crossover investor in Europe dedicated to late-stage biopharma and medtech investments.”

They got a leg up in France after winning a special “Tibi” designation from the French government, giving them access to a pool of €6 billion that helped them gain an edge with institutional investors. Since they were founded close to 50 years ago, the venture group has backed more than 500 companies and currently has more than €2 billion under management.

Thank you, next: Take­da hands Ovid $196M cash to rein back in Phase III-ready seizure drug, re­viv­ing bat­tered stock

Soticlestat made it.

Takeda is bringing the drug back into its fold more than four years after first entrusting the team at Ovid with the mid-stage clinical work. For all that — generating what they saw as positive Phase II data in Dravet syndrome and Lennox-Gastaut syndrome — the biotech has been rewarded with $196 million in upfront cash, with another $660 million reserved for regulatory and commercial milestones.

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Michael Shpigelmacher

Khosla joins bet on un­con­ven­tion­al start­up look­ing to send drug de­liv­er­ing ro­bots in­to the brain

When Michael Shpigelmacher started the project, he knew he’d have to fund it himself. Every other effort of its kind was academic, rejected as too risky by investors.

Shpigelmacher, a robotics geek and entrepreneur who had drifted into consulting for pharma, wanted to build the real-life equivalent of technology from the 1960s film “Fantastic Voyage,” the one where a submarine crew is shrunk to “about the size of a microbe” and sent on a mission to repair a scientist’s brain. He scanned the literature, found the lab that was working on the most advanced project — at the Max Planck Institute in Germany, it turned out — and started funding them with money from his and his co-founders’ own accounts, along with some seed cash from friends and family.