An au­toim­mune up­start turns PD-L1 around to blaze a new ap­proach to di­a­betes, mul­ti­ple scle­ro­sis

PD-L1 has be­come one of the most fa­mil­iar tar­gets in the glob­al can­cer re­search world, a key play­er in me­di­at­ing a co­or­di­nat­ed im­mune sys­tem as­sault on can­cer cells. 

But what if you could al­so turn it around, use el­e­vat­ed PD-L1 to muf­fle an au­toim­mune re­sponse by T cells, hit­ting the brakes on the im­mune sys­tem and avoid­ing an as­sault on healthy tis­sue — rather than tak­ing your foot off the brake and tar­get­ing can­cer­ous cells?

A promi­nent Ital­ian in­ves­ti­ga­tor named Pao­lo Fio­r­i­na based, in part, at Boston Chil­dren’s put that idea to the test in PD-L1 de­fi­cient mice last year — adapt­ing blood stem cells — and found that it could co­or­di­nate an ef­fec­tive re­ver­sal of hy­per­glycemia and Type 1 di­a­betes, the in­her­it­ed form of the dis­ease in which the im­mune sys­tem at­tacks in­sulin-pro­duc­ing cells in the pan­creas.

He pub­lished his work in Sci­ence Trans­la­tion­al Med­i­cine.

In this case, Fio­r­i­na and his team used dif­fer­ent ap­proach­es, one of which in­volved de­liv­er­ing a gene with a healthy copy of PD-L1 in­to stem cells to reengi­neer them for a new role play­ing de­fense. Now, they’re us­ing that suc­cess­ful an­i­mal ex­per­i­ment to start a new biotech — dubbed Al­theia Sci­ence — which will look to try it in hu­mans in about 2.5 to 3 years.

Pao­lo Riz­zar­di

This isn’t the first time di­a­betes has been cured in mice. Hu­mans still face plen­ty of ob­sta­cles, so some healthy skep­ti­cism is al­ways war­rant­ed. But Pao­lo Riz­zar­di, who heads up the Mi­lan-based tech trans­fer group Au­ro­rA-TT, is a be­liev­er. 

Riz­zar­di has just lined up an $11 mil­lion launch round to com­plete the trans­la­tion­al work need­ed to de­vel­op an ef­fec­tive, com­mer­cial­ly vi­able, gene ther­a­py ap­proach that could adapt pa­tient stem cells to do the work with PD-L1.

“I like the idea,” Riz­zar­di tells me. “The con­cept was quite sim­ple,” where the sci­en­tists rec­og­nized a com­mon bi­o­log­ic mech­a­nism that worked across mul­ti­ple in­di­ca­tions.

And they are by no means lim­it­ing the ap­proach to di­a­betes. Al­theia’s team is work­ing on the be­lief that mul­ti­ple scle­ro­sis should be an ear­ly fo­cus at the com­pa­ny. And rheuma­toid arthri­tis as well as oth­er au­toim­mune con­di­tions could be added lat­er.

Di­a­betes, MS, rheuma­toid arthri­tis; these are all dis­eases with ma­jor pop­u­la­tions. But Riz­zar­di be­lieves that the ex­perts in the field are giv­ing birth to gen­er­a­tion 2.0 of gene ther­a­py, which can be adapt­ed to large num­bers with an econ­o­my of scale.

Mi­lan, which was home to the gene ther­a­py work that Glax­o­SmithK­line re­cent­ly spun out to Or­chard, has a broad group of ex­perts in gene ther­a­py op­er­at­ing at the San Raf­faele Sci­en­tif­ic In­sti­tute. But with gene ther­a­py ex­per­tise lined up along the East Coast, a group of po­ten­tial part­ners along with in­vestors who are hap­py to back pre­clin­i­cal work like this, Riz­zar­di felt the 3-mem­ber team do­ing the ini­tial work should have an of­fice in New York.

Some pri­vate in­vestors joined the Rovati fam­i­ly’s Fidim/Rot­tapharm Biotech group in pro­vid­ing the first $11 mil­lion, which could range up to $17 mil­lion as the project de­vel­ops.

“These num­bers are not that fas­ci­nat­ing for the US,” Riz­zar­di read­i­ly con­cedes, but they are “pret­ty good” for Eu­rope. And it’s enough for a lean-and-mean team to get through the proof-of-con­cept stage for this, when they’ll know if they have some­thing that could com­plete­ly dis­rupt ma­jor mar­kets.

That’s pret­ty good, too.

Hal Barron, GSK

Break­ing the death spi­ral: Hal Bar­ron talks about trans­form­ing the mori­bund R&D cul­ture at GSK in a crit­i­cal year for the late-stage pipeline

Just ahead of GlaxoSmithKline’s Q2 update on Wednesday, science chief Hal Barron is making the rounds to talk up the pharma giant’s late-stage strategy as the top execs continue to woo back a deeply skeptical investor group while pushing through a whole new R&D culture.

And that’s not easy, Barron is quick to note. He told the Financial Times:

I think that culture, to some extent, is as hard, in fact even harder, than doing the science.

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UP­DAT­ED: Stay tuned: Bio­gen’s num­bers are great — it’s their wor­ri­some fu­ture that leaves an­a­lysts skit­tish

Biogen came out with an upbeat assessment of their Q2 numbers today, discounting the arrival of a key rival for its blockbuster Spinraza franchise. But the top execs remain grimly determined to not say much anything new about the sore points that have dragged down its stock, including the future of its big investment in Alzheimer’s or how it plans to invest the considerable cash that the big biotech continues to reap.

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Why wait? Cel­gene re­struc­tures a big Jounce pact — ze­ro­ing in on new I/O path­way with $530M deal and bump­ing ICOS

Celgene’s business team isn’t waiting for the big merger with Bristol-Myers Squibb to go through before syncing its strategy with the new mother ship.

Tuesday evening the big biotech unveiled a $530 million deal — $50 million in upfront cash — to amend their alliance with Jounce Therapeutics $JNCE to gain worldwide rights to JTX-8064, an antibody that targets the LILRB2 receptor on macrophages. Their old, $2.6 billion deal is being scrapped, leaving Jounce with a pipeline that includes the lead drug, the ICOS-targeting vopratelimab.

PACT Phar­ma says it's per­fect­ed the tech to se­lect neoanti­gens for per­son­al­ized ther­a­py — now on­to the clin­ic

At PACT Pharma, the lofty goal to unleash a “tsunami” of T cells personalized for each patient has hinged on the ability to correctly identify the neoantigens that form something of a fingerprint for each tumor, and extract the small group of T cells primed to attack the cancer. It still has a long way to go testing a treatment in humans, but the biotech says it has nailed that highly technical piece of the process.

UP­DAT­ED: My­ovan­t's uter­ine fi­broid drug looks com­pet­i­tive in PhI­II — but can they van­quish mighty Ab­b­Vie?

Vivek Ramaswamy’s Myovant $MYOV has closely matched its positive first round of Phase III data for their uterine fibroid drug relugolix, setting up a head-to-head rivalry with pharma giant AbbVie as the little biotech steers to the market with a planned filing in Q4.

Here’s how Myovant plans to prevail over the AbbVie $ABBV empire.

In the study, 71.2% of women receiving once-daily relugolix combination therapy achieved the clinical response they were looking for, compared to only 14.7% in the control arm. The data comfortably reflected the same outcomes in the first Phase III — 73.4% of women receiving once-daily oral relugolix combination therapy achieved the responder criteria compared with 18.9% of women receiving placebo — which will reassure regulators that they are getting the carefully randomized data that qualifies for the FDA’s gold standard for success.

Lit­tle Mar­i­nus sees its shares eclipsed as the Sage ri­val fails to com­pare on PPD in PhII

The executive team at Sage $SAGE have skirted another potential pitfall on its way to racking up a big future for its depression drug Zulresso.

Little Marinus Pharmaceuticals $MRNS had sought to challenge the Sage drug with an IV formulation — followed by an oral version — of ganaxolone for postpartum depression. But researchers say their Phase II study failed to positively differentiate itself from a placebo at 28 days — leaving them to hold up “clinically meaningful” data within the first day of administration compared to the control arm.

Roche cuts loose Tam­i­flu OTC rights, hand­ing Sanofi the keys as the phar­ma gi­ant dou­bles down on Xofluza

Roche set out to make a better flu medicine than Tamiflu as that franchise was headed to a generic showdown. Now they’ll see just how well Xofluza stacks up against the mainstay drug after handing off over-the-counter rights in the US to Sanofi.

Sanofi $SNY says it will now step in to negotiate a deal with the FDA to steer Tamiflu into the OTC market, a role that could well involve new studies to ease passage of the drug out of doctor’s hands and into the consumer end of the market. And the French pharma giant will have first dibs over “selected” OTC markets around the world as they push ahead.

Aca­dia is mak­ing the best of it, but their lat­est PhI­II Nu­plazid study is a bust

Acadia’s late-stage program to widen the commercial prospects for Nuplazid has hit a wall. The biotech reported that their Phase III ENHANCE trial flat failed. And while they $ACAD did their best to cherry pick positive data wherever they can be found, this is a clear setback for the biotech.

With close to 400 patients enrolled, researchers said the drug flunked the primary endpoint as an adjunctive therapy for patients with an inadequate response to antipsychotic therapy. The p-value was an ugly 0.0940 on the Positive and Negative Syndrome Scale, which the company called out as a positive trend.

Their shares slid 12% on the news, good for a $426 million hit on a $3.7 billion market cap at close.

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Some Big Phar­mas stepped up their game on da­ta trans­paren­cy — but which flunked the test?

The nonprofit Bioethics International has come out with their latest scorecard on data transparency among the big biopharmas in the industry — flagging a few standouts while spotlighting some laggards who are continuing to underperform.

Now in its third year, the nonprofit created a new set of standards with Yale School of Medicine and Stanford Law School to evaluate the track record on trial registration, results reporting, publication and data-sharing practice.