Eli Lil­ly jumps in­to a $473M hunt with Sig­ilon for the Holy Grail in di­a­betes cell ther­a­pies

Stem cell ther­a­pies have gone through every stage of the long and painful hype cy­cle for emerg­ing drug tech­nolo­gies: Start­ing with wild­ly in­flat­ed ear­ly ex­pec­ta­tions through bit­ter dis­il­lu­sion­ment, a trough of de­spair and on to a slow and pa­tient re­cov­ery brought about by years of dili­gent re­search work in the lab.

Paul Wot­ton, who’s seen it all, be­lieves he can now see the off-the-shelf cell prod­ucts of the fu­ture — en­cap­su­lat­ed in what they’ve dubbed Afi­bromer plat­form tech — tak­ing shape at the end of the new­ly ris­ing curve.

As the found­ing CEO at Flag­ship-seed­ed Sig­ilon, a start­up launched last year in Cam­bridge, MA with a $23.5 mil­lion round, he’s now un­veil­ing one of the fi­nal re­main­ing pieces nec­es­sary for a come­back: An al­liance with a Big Phar­ma part­ner.

To­day Sig­ilon is an­nounc­ing a $473 mil­lion pact with Eli Lil­ly — which is step­ping out un­der a bold­er R&D chief in Dan Skovron­sky — to dri­ve their stem cell work on Type 1 di­a­betes in­to the clin­ic, with $63 mil­lion of that in an up­front and the rest divvied up with a goal of ful­ly fund­ing the de­vel­op­ment of a durable new ther­a­py for the dis­ease. Eli Lil­ly is al­so mak­ing an undis­closed eq­ui­ty in­vest­ment in the com­pa­ny.

“I think we’ve kind of dis­cov­ered the Holy Grail to make cell ther­a­py a re­al­i­ty,” says Wot­ton. 

While re­searchers fig­ured out a long time ago how to get stem cells to trans­form in­to in­sulin pro­duc­ing pan­cre­at­ic be­ta cells for di­a­bet­ics, get­ting them in­to the body to do their work with­out trig­ger­ing a se­vere im­mune re­ac­tion has been an in­sur­mount­able ob­sta­cle.

Bob Langer

But af­ter test­ing new tech out of the labs of MIT’s Bob Langer and Daniel An­der­son in ro­dents as well as non-hu­man pri­mates, Sig­ilon be­lieves it’s with­in a cou­ple of years of start­ing work on a hu­man clin­i­cal tri­al — a ma­jor step to­ward ob­tain­ing clear proof-of-con­cept da­ta. They be­lieve they can de­liv­er islet cells to the body, and keep it hid­den from the im­mune sys­tem, pre­vent­ing fi­bro­sis that can choke cells of nu­tri­tion and oxy­gen. And while they are now pi­o­neer­ing a ground­break­ing field, there are sol­id pre­clin­i­cal rea­sons to be­lieve that they can make the hur­dle in hu­mans.

“Bob Langer’s team screened 600 mol­e­cules that could evade the im­mune sys­tem,” says Wot­ton. And they be­lieve they are on to the kind of en­cap­su­lat­ed cell-based ther­a­pies that can be de­liv­ered in wa­ter sol­u­ble poly­mers — Langer’s sweet spot in the lab — nec­es­sary for de­vis­ing a ther­a­py that could cre­ate a re­li­able sup­ply of in­sulin for pa­tients.

They’re not alone here. Har­vard spin­out Sem­ma re­cent­ly gar­nered a $114 mil­lion megaround to see if their “tea bag” tech for pro­duc­ing in­sulin can do the same thing.

It won’t be quick. There’s no hard time­line on the di­a­betes side, but Sig­ilon is with­in a cou­ple of years of mov­ing a pro­gram in­to the clin­ic us­ing the same tech plat­form to spawn fac­tor VI­II and IX for he­mo­phil­ia pa­tients. And that could help pave the way to a clin­i­cal study in di­a­betes soon af­ter.

“What we have is plat­form tech­nol­o­gy that you can ap­ply to any al­lo­gene­ic (off the shelf) cell line,” says Wot­ton, “pro­gram cells to man­u­fac­ture fac­tor VI­II or IX, or man­u­fac­ture an­ti­bod­ies, with an abil­i­ty to avoid de­tec­tion of the im­mune sys­tem.”

One way to think of it, he says, is as a kind of “gene ther­a­py in a box,” able to ex­press two pro­teins with an op­tion of top­ping up the dose if need­ed lat­er.

How long will that kind of ther­a­py last? Wot­ton doesn’t know the an­swer to that yet, but he’s gam­bling that it’s years rather than months. And Eli Lil­ly, which is in­creas­ing their bet on bold re­search gam­bles, wants to come along for the ride.

This is a big deal for the cell ther­a­py field in re­gen­er­a­tive med­i­cine, as the big play­ers large­ly bowed out of the are­na years ago, sat­is­fied that they were far, far away from any com­mer­cial pro­grams. Eli Lil­ly’s re­turn, along­side a same-day move by Roche we are re­port­ing now, could be an­oth­er sign that the hype cy­cle is fi­nal­ly en­ter­ing the be­gin­ning of the end.

De­vel­op­ment of the Next Gen­er­a­tion NKG2D CAR T-cell Man­u­fac­tur­ing Process

Celyad’s view on developing and delivering a CAR T-cell therapy with multi-tumor specificity combined with cell manufacturing success
Overview
Transitioning potential therapeutic assets from academia into the commercial environment is an exercise that is largely underappreciated by stakeholders, except for drug developers themselves. The promise of preclinical or early clinical results drives enthusiasm, but the pragmatic delivery of a therapy outside of small, local testing is most often a major challenge for drug developers especially, including among other things, the manufacturing challenges that surround the production of just-in-time and personalized autologous cell therapy products.

Paul Hudson, Getty Images

UP­DAT­ED: Sanofi CEO Hud­son lays out new R&D fo­cus — chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

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Roger Perlmutter, Merck

#ASH19: Here’s why Mer­ck is pay­ing $2.7B to­day to grab Ar­Qule and its next-gen BTK drug, lin­ing up Eli Lil­ly ri­val­ry

Just a few months after making a splash at the European Hematology Association scientific confab with an early snapshot of positive data for their BTK inhibitor ARQ 531, ArQule has won a $2.7 billion buyout deal from Merck.

Merck is scooping up a next-gen BTK drug — which is making a splash at ASH today — from ArQule in an M&A pact set at $20 a share $ARQL. That’s more than twice Friday’s $9.66 close. And Merck R&D chief Roger Perlmutter heralded a deal that nets “multiple clinical-stage oral kinase inhibitors.”

This is the second biotech buyout pact today, marking a brisk tempo of M&A deals in the lead-up to the big JP Morgan gathering in mid-January. It’s no surprise the acquisitions are both for cancer drugs, where Sanofi will try to make its mark while Merck beefs up a stellar oncology franchise. And bolt-ons are all the rage at the major pharma players, which you could also see in Novartis’ recent $9.7 billion MedCo buyout.

ArQule — which comes out on top after their original lead drug foundered in Phase III — highlighted early data on ‘531 at EHA from a group of 6 chronic lymphocytic leukemia patients who got the 65 mg dose. Four of them experienced a partial response — a big advance for a company that failed with earlier attempts.

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Paul Hudson, Sanofi

Paul Hud­son promis­es a bright new fu­ture at Sanofi, kick­ing loose me-too drugs and fo­cus­ing on land­mark ad­vances. But can he de­liv­er?

Paul Hudson was on a mission Tuesday morning as he stood up to address Sanofi’s new R&D and business strategy.

Still fresh into the job, the new CEO set out to convince his audience — including the legions of nervous staffers inevitably devoting much of their day to listening in — that the pharma giant is shedding the layers of bureaucracy that had held them back from making progress in the past, dropping the duds in the pipeline and reprioritizing a more narrow set of experimental drugs that were promised as first-in-class or best-in-class.  The company, he added, is now positioned to “go after other opportunities” that could offer a transformational approach to treating its core diseases.

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Left top to right: Mark Timney, Alex Denner, Vas Narasimhan. (The Medicines Company, Getty, AP/Endpoints News)

In a play-by-play of the $9.7B Med­Co buy­out, No­var­tis ad­mits it over­paid while of­fer­ing a huge wind­fall to ex­ecs

A month into his tenure at The Medicines Company, new CEO Mark Timney reached out to then-Novartis pharma chief Paul Hudson: Any interest in a partnership?

No, Hudson told him. Not now, at least.

Ten months later, Hudson had left to run Sanofi and Novartis CEO Vas Narasimhan was paying $9.7 billion for the one-drug biotech – the largest in the string of acquisitions Narasimhan has signed since his 2017 appointment.

The deal was the product of an activist investor and his controversial partner working through nearly a year of cat-and-mouse negotiations to secure a deal with Big Pharma’s most expansionist executive. It represented a huge bet in a cardiovascular field that already saw two major busts in recent years and brought massive returns for two of the industry’s most eye-raising names.

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Am­gen puts its foot down in shiny new South San Fran­cis­co hub as it re­or­ga­nizes R&D ops

Amgen has signed up to be AbbVie’s neighbor in South San Francisco as it moves into a nine-story R&D facility in the booming biotech hub.

The arrangement gives Amgen 240,000 square feet of space on the Gateway of Pacific Campus, just a few minutes drive from its current digs at Oyster Point. The new hub will open in 2022 and house the big biotech’s Bay Area employees working on cardiometabolic, inflammation and oncology research.

Ab­b­Vie, Scripps ex­pand part­ner­ship, for­ti­fy fo­cus on can­cer drugs

Scripps and AbbVie go way back. Research conducted in the lab of Scripps scientist Richard Lerner led to the discovery of Humira. The antibody, approved by the FDA in 2002 and sold by AbbVie, went on to become the world’s bestselling treatment. In 2018, the drugmaker and the non-profit organization signed a pact focused on developing cancer treatments — and now, the scope of that partnership has broadened to encompass a range of diseases, including immunological and neurological conditions.

South Ko­rea jails 3 Sam­sung ex­ecs for de­stroy­ing ev­i­dence in Bi­o­Log­ics probe

Three Samsung executives in Korea are going to jail.

The convictions came in what prosecutors had billed as “biggest crime of evidence destruction in the history of South Korea”: a case of alleged corporate intrigue that was thrown open when investigators found what was hidden beneath the floor of a Samsung BioLogics plant. Eight employees in total were found guilty of evidence tampering and the three executives were each sentenced to up to two years in prison.

Nick Plugis, Avak Kahvejian, Cristina Rondinone, Milind Kamkolkar and Chad Nusbaum. (Cellarity)

Cel­lar­i­ty, Flag­ship's $50M bet on net­work bi­ol­o­gy, mar­ries ma­chine learn­ing and sin­gle-cell tech for drug dis­cov­ery

Cellarity started with a simple — but far from easy — idea that Avak Kahvejian and his team were floating around at Flagship Pioneering: to digitally encode a cell.

As he and his senior associate Nick Plugis dug deeper into the concept, they found that most of the models others have developed take a bottom-up approach, where they assemble the molecules inside cells and the connections between them from scratch. What if they opt for a top-down approach, aided by single-cell transcriptomics and machine learning, to gauge the behavior of the entire cellular network?