Ron Evans (Salk Institute)

Ron Evans steals a trick from I/O, and points the way to a trans­for­ma­tion­al di­a­betes ther­a­py

Salk In­sti­tute sci­en­tist and se­r­i­al biotech en­tre­pre­neur Ron Evans showed new mouse work yes­ter­day that could point to a long-sought holy grail for di­a­betes treat­ment.

The study, pub­lished in Na­ture, in­volved a new ap­proach for islet cell trans­plant, a di­a­betes ther­a­py where dys­func­tion­al in­sulin-pro­duc­ing cells on the pan­creas are re­placed with func­tion­al ones. The treat­ment has been around for a while and new ones are in de­vel­op­ment, but they’ve been ham­pered by the fact that pa­tients will re­ject the cells un­less they go on im­muno-sup­pres­sive drugs.

But, work­ing with iP­SC stem cells and tricks from im­munother­a­py, Evans and his team de­vel­oped what they called “im­mune-eva­sive” clus­ters of cells — es­sen­tial­ly mi­ni pan­creas­es. Placed in­to mice, these cells se­cret­ed prop­er amounts of in­sulin with­out com­ing un­der fire from im­mune cells, point­ing the way to­ward a sim­i­lar ap­proach in hu­mans.

“Most type 1 di­a­bet­ics are chil­dren and teenagers,” Evans said in a state­ment. “We hope that re­gen­er­a­tive med­i­cine in com­bi­na­tion with im­mune shield­ing can make a re­al dif­fer­ence in the field by re­plac­ing dam­aged cells with lab-gen­er­at­ed hu­man islet-like cell clus­ters that pro­duce nor­mal amounts of in­sulin on de­mand.”

Evans, who most re­cent­ly co-found­ed and sold to Astel­las the “ex­er­cise-in-a-pill” biotech Mi­to­bridge, and his co-au­thors are hard­ly alone in this race. Vi­a­Cyte has re­ceived ma­jor back­ing from both pri­vate donors and the Ju­ve­nile Di­a­betes Re­search Foun­da­tion for their own stem cell-de­rived islet cell trans­plant. Flag­ship al­so launched Sig­ilon ear­li­er this year with $80.3 mil­lion in Se­ries B fund­ing. With tech­nol­o­gy from Robert Langer, the com­pa­ny is de­vel­op­ing poly­mers that can en­case cells for trans­plant. A di­a­betes pro­gram is in the IND-en­abling phase with Eli Lil­ly.

Four years ago, Evans and his team fig­ured out how to make func­tion­al pan­cre­at­ic be­ta cells for the first time, us­ing a se­ries of mol­e­c­u­lar switch­es to get them to not on­ly pro­duce in­sulin but do so in re­sponse to glu­cose, as nor­mal cells do. But that still left ques­tions about how to go from in­di­vid­ual cells in­to pan­creas-like clus­ters, and how to get those cells to avoid the im­mune sys­tem when trans­plant­ed.

To clus­ter the cells, Evans’ lab fig­ured out that a pro­tein in­volved in em­bry­on­ic de­vel­op­ment called WNT4 could trig­ger the same mol­e­c­u­lar mech­a­nisms that cre­at­ed the func­tion­al be­ta cells. Adding that pro­tein led to the cre­ation of 3-D clus­ters of cells sim­i­lar to what would be seen in a hu­mans. They called them hu­man islet-like organoids, or HI­LOs.

Evans, with Downes and Yoshi­hara

To make those organoids, Evans and Ei­ji Yoshi­hara, a sci­en­tist in his lab, stole a trick from an­oth­er field: im­muno-on­col­o­gy. Us­ing short puls­es of a pro­tein called in­ter­fer­on gam­ma, Yoshi­hara got the cells to ex­press PD-L1.

The PD-L1 had the op­po­site ef­fect of the PD-L1 in­hibitors used in can­cer. Rather than mak­ing sure T cells saw a tu­mor, they made sure T cells didn’t see the islet cells.

“This is the first study to show that you can pro­tect HI­LOs from the im­mune sys­tem with­out ge­net­ic ma­nip­u­la­tion,” Michael Downes, an au­thor on the pa­per, said. “If we are able to de­vel­op this as a ther­a­py, pa­tients will not need to take im­mune-sup­press­ing drugs.”

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

Vas Narasimhan (AP Images)

UP­DAT­ED: Still held down by clin­i­cal hold, No­var­tis' Zol­gens­ma falls fur­ther be­hind Bio­gen and Roche as FDA asks for a new piv­otal study

Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 90,400+ biopharma pros reading Endpoints daily — and it's free.

FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials, and could help shore up public trust in the agency and any eventual vaccine.

PhII Alzheimer's fail­ure deals new blow to Roche, AC Im­mune — but the tau hy­poth­e­sis is far from dead

The leading anti-tau antibody has failed its first Phase II testing, casting a shadow on a popular target (just trailing amyloid beta) for Alzheimer’s disease.

Roche and AC Immune are quick to acknowledge disappointment in the topline readout, which suggested that semorinemab did not reduce cognitive decline among patients with early Alzheimer’s disease, who are either just starting to have symptoms or have mild manifestations.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 90,400+ biopharma pros reading Endpoints daily — and it's free.

Covid-19 roundup: J&J be­gins piv­otal Phase III tri­al for vac­cine; Con­tro­ver­sial hu­man chal­lenge tri­als to be­gin in Lon­don — re­port

Johnson & Johnson announced it’s beginning a pivotal Phase III trial for its Covid-19 candidate, JNJ-78436735 — the first single-dose vaccine in this stage.

The Phase III trial, dubbed ENSEMBLE, will enroll 60,000 patients worldwide, making it the largest Phase III study of a Covid-19 vaccine to date. J&J said the candidate achieved positive interim results in a Phase I/IIa study, which will be published “imminently.” There’s a possibility that the first batches will be ready for potential emergency use in early 2021, according to the company.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 90,400+ biopharma pros reading Endpoints daily — and it's free.

Patrick Enright, Longitude co-founder (Longitude)

As its biotechs hit the pan­dem­ic ex­it, Lon­gi­tude rais­es $585M for new neu­ro, can­cer, ag­ing and or­phan-fo­cused fund

The years have been kind to Longitude Capital. This year, too.

A 2006 spinout of Pequot Capital, its founders started their new firm just four years before the parent company would go under amid insider trading allegations. Their first life sciences fund raised $325 million amid the financial crisis, they added a second for $385 million and then in, 2016, a third for $525 million. In the last few months, the pandemic biotech IPO boom netted several high-value exits from those funds, as Checkmate, Vaxcyte, Inozyme and Poseida all went public.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 90,400+ biopharma pros reading Endpoints daily — and it's free.

Gene Wang, Immetas co-founder and CEO (file photo)

Im­metas Ther­a­peu­tics nabs $11M Se­ries A to nar­row their bis­pe­cif­ic work tar­get­ing in­flam­ma­tion in age-re­lat­ed dis­eases

How does a biotech celebrate its two-year anniversary? For Immetas Therapeutics, it’s with an $11 million Series A round and a game plan to fight age-related disease.

Co-founders Gene Wang and David Sinclair came together years ago around the idea that inflammation is the ultimate process driving age-related illnesses, including cancer. The duo launched Immetas in 2018 and packed the staff with industry experts. Wang, who says he’s always had an entrepreneurial spirit, has held lead roles at Novartis, GSK, Bristol Myers Squibb and Merck. He’s worked on blockbuster drugs like Humira, Gardasil, Varubi and Zolinza. And now, he’s channeling that spirit as CEO.

Scoop: ARCH’s Bob Nelsen is back­ing an mR­NA up­start that promis­es to up­end the en­tire man­u­fac­tur­ing side of the glob­al busi­ness

For the past 2 years, serial entrepreneur Igor Khandros relied on a small network of friends and close insiders to supply the first millions he needed to fund a secretive project to master a new approach to manufacturing mRNA therapies.

Right now, he says, he has a working “GMP-in-a-box” prototype for a new company he’s building — after launching 3 public companies — which plans to spread this contained, precise manufacturing tech around the world with a set of partners. He’s raised $60 million, recruited some prominent experts. And not coincidentally, he’s going semi-public with this just as a small group of pioneers appears to be on the threshold of ushering in the world’s first mRNA vaccines to fight a worldwide pandemic.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

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.