Flag­ship’s Sig­ilon grabs $80M to bring Robert Langer cell ther­a­py tech in­to the clin­ic

Roge­rio Vi­val­di had nev­er giv­en much thought to in­dus­try.

A new­ly mint­ed MD, he was work­ing at a hos­pi­tal in Rio De Janeiro when one of his pro­fes­sors asked if he might take on a case that re­quired con­sis­tent fol­low-up: A 14-year-old boy with Gauch­er’s, a rare ge­net­ic dis­or­der that meant he was miss­ing a key en­zyme of­ten called the cell’s re­cy­cling sys­tem. He had come in with en­larged or­gans and stunt­ed growth.

Roge­rio Vi­val­di

But the par­ents were in­ter­est­ed in try­ing a new treat­ment in­tro­duced that year, 1991, from Gen­zyme, one of the first ma­jor rare dis­ease biotechs. It would re­place the miss­ing en­zyme with a re­com­bi­nant form. Vi­val­di took the case. The boy re­cov­ered. He’s now 41, Vi­val­di said, with two kids.

“Usu­al­ly, I de­scribe that mo­ment as trans­form­ing the pa­tient’s life,” Vi­val­di told End­points News. “What peo­ple don’t re­al­ize is that mo­ment al­so changed my life. I had no thought of go­ing in­to biotech. I was a clin­i­cian.”

Vi­val­di, though, would soon take a job at Gen­zyme and then a se­ries of biotech C-suites be­fore Flag­ship tapped him 2 years ago to lead one of its new­er biotechs: Sig­ilon Ther­a­peu­tics. And to­day, he’s help­ing piv­ot the com­pa­ny to­ward the clin­ic for the first of sev­er­al chron­ic ill­ness­es, an­nounc­ing an $80.3 mil­lion Se­ries B fi­nanc­ing that will help push their lead drug in­to hu­man test­ing.

“It’s kind of the physi­cian ex­pe­ri­ence with the pa­tient ex­pe­ri­ence: What should we do — as a new class of med­i­cines — to re­al­ly bring a func­tion­al cure for pa­tients with chron­ic dis­eases?” Vi­val­di said, cit­ing his work with en­zyme ther­a­py and his own ex­pe­ri­ence with type 1 di­a­betes.

Sig­ilon’s plat­form comes out of work from Robert Langer’s and Daniel An­der­son’s labs at MIT and sev­er­al grants from the Ju­ve­nile Di­a­betes Re­search Foun­da­tion. For years, biotech and aca­d­e­m­ic re­searchers have known that a form of cell ther­a­py known as islet cell trans­plant could of­fer a po­ten­tial func­tion­al cure to di­a­betes, al­low­ing a pa­tient’s pan­creas to once again pump out prop­er dos­es of in­sulin.

The prob­lem, Vi­val­di said, is that the body’s im­mune sys­tem tends to at­tack these new cells, cov­er­ing it in fi­brot­ic scar tis­sue and ren­der­ing it non-func­tion­al. The few hun­dred pa­tients to re­ceive the trans­plant in the last 20 years have had to take ex­ten­sive dos­es of im­muno-sup­pres­sives. One way re­searchers long the­o­rized you could avoid these is­sues was by en­cap­su­lat­ing the cells in poly­mers — like mi­cro­scop­ic space suits. In 2016, Langer and An­der­son made it work, at least in the lab, and launched Sig­ilon with Flag­ship.

“It cre­ates a sphere or cap­sule where you could put many cells — be­tween 25 and 45,000 cells in one sin­gle 1.5 mil­ligram di­am­e­ter,” Vi­val­di said. “We cre­ate a space where the cells can be pro­duc­ing what­ev­er we en­gi­neer the cells to pro­duce.”

In 2018, Eli Lil­ly signed on to Sig­ilon’s di­a­betes pro­gram for $63 mil­lion up­front and $410 mil­lion in mile­stones. Sig­ilon in­sists, though, that the plat­form is much broad­er. The first clin­i­cal in­di­ca­tion will come lat­er this year in he­mo­phil­ia A be­cause, Vi­val­di said, it’s eas­i­er to see they are get­ting ac­tiv­i­ty in the blood rather than tis­sue. Be­yond that, there are pro­grams in he­mo­phil­ia B and even a pair of lyso­so­mal dis­or­ders — the same cat­e­go­ry as Gauch­er’s — that have not proven as sus­cep­ti­ble to en­zyme re­place­ment ther­a­py.

They won’t be alone in com­pet­ing on any of those in­di­ca­tions. Oth­er com­pa­nies, such as Vi­a­cyte, are us­ing oth­er meth­ods to get islet trans­plants to work, in­clud­ing by us­ing pluripo­tent stem cells. And gene ther­a­py is in ear­ly de­vel­op­ment for he­mo­phil­ia, lyso­so­mal dis­or­ders and even di­a­betes. Vi­val­di, though, said they can use their ther­a­py in far more pa­tients. Some pa­tients can’t get AAV, the vec­tor used in most gene ther­a­pies, he not­ed, and gene ther­a­py is gen­er­al­ly for pa­tients with more dire prog­noses, as op­posed to rel­a­tive­ly healthy ones.

“The le­git­i­ma­cy of our tech­nol­o­gy is much broad­er,” Vi­val­di said.

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Pfiz­er's big block­buster Xel­janz flunks its post-mar­ket­ing safe­ty study, re­new­ing harsh ques­tions for JAK class

When the FDA approved Pfizer’s JAK inhibitor Xeljanz for rheumatoid arthritis in 2012, they slapped on a black box warning for a laundry list of adverse events and required the New York drugmaker to run a long-term safety study.

That study has since become a consistent headache for Pfizer and their blockbuster molecule. Last year, Pfizer dropped the entire high dose cohort after an independent monitoring board found more patients died in that group than in the low dose arm or a control arm of patients who received one of two TNF inhibitors, Enbrel or Humira.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 99,000+ biopharma pros reading Endpoints daily — and it's free.

Top gene ther­a­py deals, M&A pacts in 2020 high­light an­oth­er big year in one of the hottest fields in bio­phar­ma

Chris Dokomajilar at DealForma has been crunching the numbers on gene therapy deals over the last 2 years and came away with a few key observations.

Both the upfront cash and deal totals last year backed off a bit from the record high hit in 2019, but the totals are still running well ahead of anything we’ve seen in the years prior to 2019/2020.
2020 R&D partnerships came in at 23 deals, with $1.1 billion in disclosed upfront cash and equity and more than $8.5 billion in total deal value. Looking at 2019-2020 M&A, Dokomajilar found: 9 Acquisitions, with over $11.1 billion in disclosed upfront cash and equity and more than $13.4 billion in total M&A value.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 99,000+ biopharma pros reading Endpoints daily — and it's free.

Bob Nelsen (Michael Kovac/Getty Images)

ARCH an­nounces largest fund yet, rais­ing $1.85B to back men­tal health, cell and gene edit­ing ap­proach­es

Nearly a year ago, as the pandemic encroached and the stock market cratered, Flagship and ARCH Venture announced three mega-funds worth a combined $2.6 billion. They wanted, ARCH’s Bob Nelsen said, to restore confidence “that there was money out there and a lot of it” to invest in biotech.

Since then, the stock market has returned — almost frighteningly so — and Nelsen has kept raising and spending cash. On Thursday, he announced a new fund, worth $1.85 billion. It’s the largest pot yet for a VC famous for its deep pockets.

Covid-19 roundup: EU and As­traZeneca trade blows over slow­downs; Un­usu­al unions pop up to test an­ti­bod­ies, vac­cines

After coming under fire for manufacturing delays last week, AstraZeneca’s feud with the European Union has spilled into the open.

The bloc accused the pharma giant on Wednesday of pulling out of a meeting to discuss cuts to its vaccine supplies, the AP reported. AstraZeneca denied the reports, saying it still planned on attending the discussion.

Early Wednesday, an EU Commission spokeswoman said that “the representative of AstraZeneca had announced this morning, had informed us this morning that their participation is not confirmed, is not happening.” But an AstraZeneca spokesperson later called the reports “not accurate.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 99,000+ biopharma pros reading Endpoints daily — and it's free.

Janet Woodcock (AP Images)

Ad­vo­ca­cy groups don't want Janet Wood­cock to head the FDA, blast­ing ‘reg­u­la­to­ry fail­ures’ in opi­oid cri­sis

It turns out the controversies around Janet Woodcock’s regulatory legacy weren’t limited to Sarepta’s eteplirsen.

A coalition of advocacy groups dedicated to the opioid crisis urged Norris Cochran and Xavier Becerra — the acting and designated HHS secretary, respectively — to keep her reign as interim FDA chief a “very short transition.” During her lengthy tenure as CDER, they add, Woodcock presided over “one of the worst regulatory agency failures in U.S. history.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 99,000+ biopharma pros reading Endpoints daily — and it's free.

Dean Li kicks off Mer­ck­'s post-Roger Perl­mut­ter era by team­ing with Arti­va and its off-the-shelf CAR-NK tech

Even though Dean Li has now officially taken over for Roger Perlmutter as R&D chief, Merck’s appetite for dealmaking continues to be ravenous.

Li struck his first big deal at the helm Thursday morning, hammering out a collaboration with Artiva Biotherapeutics that could earn the biotech nearly $1.9 billion when all is said and done. It’s a quick rise and validation for Artiva, which just last June launched with a $78 million Series A.

Take­da earns win for its TKI in­hibitor in tiny lung can­cer group — but GI side ef­fects could be an ear­ly red flag

Japanese drugmaker Takeda has made a big push in recent years to build a hand in oncology, particularly in the next-gen cancer space. One of those candidates, tyrosine kinase inhibitor (TKI) mobocertinib, recently earned the FDA’s interest in a small section of untreated lung cancer patients, but will severe GI side effects be a roadblock?

Takeda’s oral mobocertinib posted clinically significant objective response rates in a Phase I/II adaptive trial drugging metastatic non-small cell lung cancer patients with EGFR exon 20 gene mutations who had previously undergone platinum-based chemotherapy, according to data presented Thursday at the virtual World Conference on Lung Cancer.

Covid-19 roundup: Con­tro­ver­sy around colchicine per­co­lates af­ter study fail­ure; As­traZeneca's meet­ing with EU was 'con­struc­tive,' but did­n't solve much

A group of researchers at the Montreal Heart Institute has spelled out what they had called positive results suggesting that colchicine, an inexpensive oral anti-inflammatory drug commonly used to treat gout, could prevent Covid-19 complications in newly diagnosed patients.

The study failed its primary endpoint. But the latest scientific debate around treatments for the coronavirus is just beginning to brew.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 99,000+ biopharma pros reading Endpoints daily — and it's free.