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.”

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,000+ biopharma pros reading Endpoints daily — and it's free.

Tom Barnes (Orna)

The mR­NA era is here. MPM be­lieves the fu­ture be­longs to oR­NA — and Big Phar­ma wants a seat at the ta­ble

If the ultra-fast clinical development of Covid-19 vaccines opened the world’s eyes to the promises of messenger RNA, the subsequent delays in supply offered a crash course on the ultra-complex process of producing them. Even before the formulation and fill-finish steps, mRNA is the precious end product from an arduous journey involving enzyme-aided transcription, modification and purification.

For Bristol Myers Squibb, Novartis Institutes for Biomedical Research, Gilead’s Kite and Astellas, it’s time to rethink the way therapeutic RNA is engineered.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,000+ biopharma pros reading Endpoints daily — and it's free.

S&P ex­pects steady ero­sion in Big Phar­ma's cred­it pro­file in 2021 as new M&A deals roll in — but don't un­der­es­ti­mate their un­der­ly­ing strength

S&P Global has taken a look at the dominant forces shaping the pharma market and come to the conclusion that there will be more downgrades than upgrades in 2021 — the 8th straight year of steady decline.

But it’s not all bad news. Some things are looking up, and there’s still plenty of money to be made in an industry that enjoys a 30% to 40% profit margin, once you factor in steep R&D expenses.

Tal Zaks, Moderna CMO (AP Photo/Rodrique Ngowi, via still image from video)

CMO Tal Zaks bids Mod­er­na a sur­prise adieu as biotech projects $18.4B in rev­enue, plots post-Covid ex­pan­sion

How do you exit a company after six years in style? Developing one of the most lucrative and life-saving products in pharma history is probably not the worst way to go.

Tal Zaks, Moderna’s CMO since 2015, will leave the mRNA biotech in September, the biotech disclosed in their annual report this morning. The company has already retained the recruitment firm Russell Reynolds to find a replacement.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,000+ biopharma pros reading Endpoints daily — and it's free.

Ken Frazier, Merck CEO (Bess Adler/Bloomberg via Getty Images)

UP­DAT­ED: Mer­ck takes a swing at the IL-2 puz­zle­box with a $1.85B play for buzzy Pan­dion and its au­toim­mune hope­fuls

When Roger Perlmutter bid farewell to Merck late last year, the drugmaker perhaps best known now for sales giant Keytruda signaled its intent to take a swing at early-stage novelty with the appointment of discovery head Dean Li. Now, Merck is signing a decent-sized check to bring an IL-2 moonshot into the fold.

Merck will shell out roughly $1.85 billion for Pandion Pharmaceuticals, a biotech hoping to gin up regulatory T cells (Tregs) to treat a range of autoimmune disorders, the drugmaker said Thursday.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,000+ biopharma pros reading Endpoints daily — and it's free.

Glax­o­SmithK­line re­thinks strat­e­gy for Covid-19 an­ti­body — not the Vir ones — af­ter tri­al flop. Is there hope in high-risk pa­tients?

In the search for a better Covid-19 therapeutic, GlaxoSmithKline and Vir have partnered up on two antibodies they hope have a chance. GSK is also testing its own in-house antibody, and early results may have shut the door on its widespread use.

A combination of GSK’s monoclonal antibody otilimab plus standard of care couldn’t best standard of care alone in preventing death and respiratory failure in hospitalized Covid-19 patients after 28 days, according to data from the Phase IIa OSCAR study unveiled Thursday.

Photo: Shutterstock

Bio­phar­ma's suc­cess rate in bring­ing drugs to mar­ket has long been abysmal. Can new tools help rewrite that trou­bled past?

In 2011, a team of researchers at British drugmaker AstraZeneca had a problem they were looking to solve.

For years, drug discovery and development were a wasteland for innovation. Novel drugs largely fell into one of two categories — monoclonal antibodies and small molecules — and new therapeutic modalities were hard to come by. After a rush of promising approvals in the late 1990s — including then-Biogen’s CD20 targeting antibody breakthrough Rituxan — the field stagnated and attrition rates stayed sky-high. What exactly is the industry doing wrong? AstraZeneca asked itself.

Endpoints Premium

Premium subscription required

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