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.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

#ES­MO20: Push­ing in­to front­line, Mer­ck and Bris­tol My­ers duke it out with new slate of GI can­cer da­ta

Having worked in parallel for years to move their respective PD-1 inhibitors up to the first-line treatment of gastrointestinal cancers, Merck and Bristol Myers Squibb finally have the data at ESMO for a showdown.

Comparing KEYNOTE-590 and CheckMate-649, of course, comes with the usual caveats. But a side-by-side look at the overall survival numbers also offer some perspective on a new frontier for the reigning checkpoint rivals, both of whom are claiming to have achieved a first.

#ES­MO20: Bris­tol My­ers marks Op­di­vo's sec­ond ad­ju­vant win — eye­ing a stan­dard of care gap

Moving into earlier and earlier treatment lines, Bristol Myers Squibb is reporting that adjuvant treatment with Opdivo has doubled the time that esophageal or gastroesophageal junction cancer patients stay free of disease.

With the CheckMate-577 data at ESMO, CMO Samit Hirawat said, the company believes it can change the treatment paradigm.

While a quarter to 30% of patients typically achieve a complete response following chemoradiation therapy and surgery, the rest do not, said Ronan Kelly of Baylor University Medical Center. The recurrence rate is also high within the first year, Hirawat added.

Clay Siegall (Life Science Washington via YouTube)

#ES­MO20: Seat­tle Ge­net­ics eyes 4th ap­proval with new da­ta in a crowd­ed field

Does Seattle Genetics have another approval on its hands?

The last 12 months, not so great for the world, has been great for Seattle Genetics. The company landed two separate FDA approvals, signed a $4.5 billion deal with Merck and watched antibody-drug conjugates — the technology they spent years developing to broad industry skepticism — emerge suddenly as one of the most popular approaches in oncology. And on Monday at ESMO, the company and their partners at Genmab unveiled the data behind the ADC it hopes will provide its next major FDA approval.

Jonathan Rigby, Immune Regulation group CEO

Im­mune Reg­u­la­tion, tak­ing two clin­i­cal pro­grams to 're­set' the im­mune sys­tem, nets $53M+ Se­ries B

A little under two years after a company rebranding, Immune Regulation is taking an even bigger step toward advancing its goals.

Formerly known as Peptinnovate, the British biotech announced a $53.4 million Series B early Monday morning, helping to further advance two clinical programs in rheumatoid arthritis and asthma. Though those are the two initial indications the company is focusing on, CEO Jonathan Rigby told Endpoints News he hopes the candidates can be applied to a broad swath of autoimmune disorders.

Israel Lowy (Regeneron)

#ES­MO20: 'As good as any PD-1 out there': Re­gen­eron flash­es PD-(L)1 lung can­cer da­ta to ri­val Mer­ck

Regeneron entered the PD-(L)1 game late, so they devised a two-pronged strategy to catch up with Big Pharma rivals: They would push it into cancers where PD-1s had yet been tested, and they would prove that it’s as powerful in the big indications as any other on the market.

They cleared a hurdle on the first goal Friday, showing a 31% response in patients with the rare skin cancer basal cell carcinoma. And with the data they’re rolling out Monday, Regeneron cancer chief Israel Lowy is ready to declare success on the second.

UP­DAT­ED: Two wild weeks for Grail end in $8B Il­lu­mi­na buy­out

Grail’s whirlwind two weeks have ended in the wealthy arms of its former founder and benefactors.

Illumina has shelled out $8 billion to reacquire the closely-watched liquid biopsy startup they spun out just 5 years ago and sold off much of its shares just 3 years ago. The deal comes nearly two weeks after the well-heeled startup filed for a potentially massive IPO — one that was disrupted just a week later when Bloomberg reported that Illumina was in talks to buy their former spinout for up to $8 billion.

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Roche vaults to the front of the NL­RP3 clin­i­cal race, pay­ing $448M up­front to bag In­fla­zome

Roche is going all in on NLRP3.

The pharma giant is putting down $448 million (€380 million) upfront to snatch Novartis-backed Inflazome, which makes it a clinical player in the space overnight.

Dublin and Cambridge, UK-based Inflazome is the second NLRP3-focused biotech Roche has acquired in less than two years, and although no numbers were disclosed in the Jecure buyout, this is almost certainly a much larger deal.

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Eli Lilly CSO Dan Skovronsky (file photo)

UP­DAT­ED: #ES­MO20: Eli Lil­ly shows off the da­ta for its Verzenio suc­cess. Was it worth $18 bil­lion?

The press release alone, devoid of any number except for the size of the trial, added nearly $20 billion to Eli Lilly’s market cap back in June. Now investors and oncologists will get to see if the data live up to the hype.

On Sunday at ESMO, Eli Lilly announced the full results for its Phase III MonarchE trial of Verzenio, showing that across over 5,000 women who had had HR+, HER2- breast cancer, the drug reduced the odds of recurrence by 25%. That meant 7.8% of the patients on the drug arm saw their cancers return within 2 years, compared with 11.3% on the placebo arm.

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