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.

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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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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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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Am­gen, Al­ler­gan biosim­i­lar of Roche's block­buster Rit­ux­an clears an­oth­er US piv­otal study 

Novartis $NVS may have given up, but Amgen $AMGN and Allergan $AGN are plowing ahead with their knockoff of Roche’s blockbuster biologic Rituxan in the United States.

Their copycat, ABP 798, was found to have a clinically equivalent impact as Rituxan — meeting the main goal of the study involving CD20-positive B-cell non-Hodgkin’s lymphoma patients. This is the second trial supporting the profile of the biosimilar. In January, it came through with positive PK results in patients with rheumatoid arthritis.

BeiGene and Mus­tang nail down spe­cial FDA sta­tus for top drugs; Roche bags added cov­er­age for Hem­li­bra

→ BeiGene $BGNE is getting a boost in its drive to field a rival to Imbruvica. The FDA has offered an accelerated review to zanubrutinib, a BTK inhibitor that has posted positive results for mantle cell lymphoma. The PDUFA date lands on February 27, 2020. The drug scored breakthrough status at the beginning of the year.

→ BeiGene isn’t the only biopharma company to gain special regulatory status today. Mustang Bio $MBIO and St. Jude Children’s Research Hospital announced that MB-107, a lentiviral gene therapy for the treatment of X-linked severe combined immunodeficiency, also known as bubble boy disease, has been granted Regenerative Medicine Advanced Therapy status.

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

UP­DAT­ED: 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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