The re­search team at the well-fund­ed Sem­ma Ther­a­peu­tics has cleared one of the last re­main­ing hur­dles to get­ting a po­ten­tial cure for di­a­betes in­to hu­man stud­ies. And if they’re right, it marks a ma­jor pre­clin­i­cal mile­stone for a resur­gent re­gen­er­a­tive med­i­cine field fo­cused on a new gen­er­a­tion of stem cell ther­a­pies.

Fe­li­cia Pagli­u­ca

Fe­li­cia Pagli­u­ca, VP of cell bi­ol­o­gy re­search and de­vel­op­ment at the Cam­bridge, MA-based biotech, told the 2019 In­ter­na­tion­al So­ci­ety for Stem Cell Re­search meet­ing in LA Sat­ur­day that their stem cell-de­rived islets per­formed as hoped for — pro­duc­ing in­sulin — in a study in­volv­ing non-hu­man pri­mates whose im­mune sys­tems had been flat­tened to pre­vent a re­jec­tion. In a sep­a­rate study in­volv­ing two pigs, a pack­age of these en­gi­neered islets con­tained in a spe­cial­ly de­signed pack­age were used suc­cess­ful­ly to gen­er­ate in­sulin with­out need­ing an im­muno­sup­pres­sant to pro­tect against a re­ac­tion.

“For the first time ever the de­vice pro­tects the cell,” Pagli­u­ca told me in a pre­view of to­day’s ses­sion, of­fer­ing ev­i­dence from a large an­i­mal mod­el that the tech­nol­o­gy func­tions with blood glu­cose lev­els, spurring in­sulin se­cre­tion as need­ed. “They re­al­ly show quite con­sis­tent re­spon­sive­ness.”

And that’s with­out fi­bro­sis, with­out cell suf­fo­ca­tion, while watch­ing the in­te­gra­tion of cell ther­a­py in­to host tis­sue.

Bas­tiano San­na

It’s ex­cit­ing, says Sem­ma CEO Bas­tiano San­na, to see the “cu­ra­tive po­ten­tial” of this cell ther­a­py.

Re­al­ly? A cure? For a mass mar­ket dis­ease like di­a­betes?

If that all seems a bit too won­der­ful to be be­lieved, think about where Pagli­u­ca is com­ing from. Stem cell ther­a­pies had their hey­day well over a decade ago as the next big thing in med­i­cine — an overnight sen­sa­tion which sput­tered out in fail­ure as the sur­vivors went back in­to the lab to do the hard work nec­es­sary to make it a re­al­i­ty. That long pe­ri­od of qui­et bred con­sid­er­able skep­ti­cism, es­pe­cial­ly af­ter the first wave of promised cures failed to ma­te­ri­al­ize. And she’s watched it play out as re­gen­er­a­tive med­i­cine made its come­back.

One of those pi­o­neer­ing sci­en­tists who stayed in the lab was Sem­ma sci­en­tif­ic founder and Har­vard pro­fes­sor Doug Melton, who pub­lished a land­mark study 5 years ago out­lin­ing how he had suc­cess­ful­ly used stem cells to cre­ate in­sulin-pro­duc­ing pan­cre­at­ic be­ta cells that were in­sert­ed in bulk in­to mice and suc­cess­ful­ly pro­tect­ed from an im­mune re­sponse — a break­through in re­gen­er­a­tive med­i­cine. And he’d been work­ing on the cure for more than 20 years, which he start­ed fol­low­ing his son’s di­ag­no­sis of Type 1 di­a­betes. 

They’ve raised $158 mil­lion over 4 years at Sem­ma to get to this stage, stand­ing on the thresh­old of a pair of small hu­man stud­ies set to launch next year. They’ll now see if they can re­pro­duce in hu­mans what they did in the non-hu­man pri­mates and pigs: first by run­ning a small study with an im­muno­sup­pres­sant, fol­lowed by the use of their de­vice in an­oth­er study lat­er next year that will avoid im­muno­sup­pres­sants.

CAR-T and gene ther­a­pies have come along to demon­strate cu­ra­tive po­ten­tial, but the CEO says it’s been frus­trat­ing to see the first wave of these ther­a­pies tar­get­ed at tiny pa­tient pop­u­la­tions. “We’re very ex­cit­ed about bring­ing the cu­ra­tive po­ten­tial of cell ther­a­pies in­to a large in­di­ca­tion.”

They’re tak­ing it step by step.

No­body is rolling out a mass tri­al for Type 2 di­a­betes. The first goal is to go af­ter some of the Type 1 di­a­betes pa­tients who are the hard­est to treat, with nowhere left to turn to rein in the au­toim­mune dis­ease. Af­ter that, they can turn to the broad­er Type 1 pop­u­la­tion be­fore mov­ing on, per­haps in­to par­tic­u­lar sub­groups of Type 2.

Ini­tial­ly, the goal will be to get the islets to do the work need­ed to safe­ly pro­duce in­sulin for these pa­tients at a re­li­able lev­el. These stem cell-de­rived islets will have to be able to be man­u­fac­tured at scale. And there’s work un­der­way to see if there’s a uni­ver­sal cell de­sign that can be used to avoid the need for the de­vice they use — some­thing Melton com­pares to a tea bag.

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

The Drugs for Neglected Diseases initiative (DNDi) and Sanofi today said that their potential sleeping sickness treatment saw success rates of up to 95% from a Phase II/III study investigating the safety and efficacy of single-dose acoziborole.

The potentially transformative treatment for sleeping sickness would mainly be targeted at African countries, according to data published today in The Lancet Infectious Diseases medical journal. The clinical trial was led by DNDi and its partners in the Democratic Republic of the Congo (DRC) and Guinea, with the authors noting: