Saar Gill at ASCO 2017 via ASH on YouTube

Ris­ing Penn star Saar Gill gets fund­ing for a next-gen CAR-T start­up, adding a new weapon to the mix

Ear­li­er this month, the Uni­ver­si­ty of Penn­syl­va­nia’s Saar Gill turned up at AS­CO to present new da­ta demon­strat­ing that a com­bi­na­tion of Im­bru­vi­ca with No­var­tis’ next-gen CAR-T CTL119 proved very ef­fec­tive in treat­ing par­tic­u­lar­ly lethal cas­es of chron­ic lym­pho­cyt­ic leukemia, wip­ing out all signs of the dis­ease in 8 of 9 treat­ment-re­sis­tant pa­tients en­rolled in an ex­plorato­ry study.

But Gill’s been par­tic­u­lar­ly busy on the CAR-T front, and not just in new re­search work. He’s al­so been en­list­ing some mar­quee in­vestors on a new start­up project that will aim at mak­ing a ma­jor new ad­vance in the field.

Close­ly in­volved with CAR-T head­lin­er Carl June in Penn’s pi­o­neer­ing work with No­var­tis, which is now rac­ing to­ward a like­ly first ap­proval, Gill’s start­up is promis­ing to com­bine the proven ef­fi­ca­cy of reengi­neered T cells with macrophages, an­oth­er weapon in the fight against can­cer that could add to the fire pow­er of the first CAR-Ts with a spe­cial fo­cus on a chal­leng­ing fron­tier: sol­id tu­mors.

“We hy­poth­e­sized ear­ly on that fo­cus­ing on dif­fer­ent ef­fec­tor cells, oth­er than T cells, might be more ef­fec­tive in try­ing to tack­le sol­id tu­mors, which has been a chal­lenge for T cell ther­a­pies. The in­nate bi­ol­o­gy drove us to try macrophages,” Gill says.

CAR-T’s first and best ap­pli­ca­tion has been cen­tered on liq­uid tu­mors, with some ma­jor ob­sta­cles to over­come in ex­pand­ing in­to sol­id tu­mors. Now Gill has some un­spec­i­fied sup­port in a new round led by Ab­b­Vie Ven­tures and Health­Cap with par­tic­i­pa­tion by Grazia Eq­ui­ty and IP Group.

Gill’s com­pa­ny is called CAR­MA — a play­ful ab­bre­vi­a­tion of the chimeric anti­gen re­cep­tors added to T cells in CAR-T along with macrophages — and it’s iden­ti­fied a lead drug called CAR­MA-0508.

“Macrophages can en­gulf and kill cells through the process of phago­cy­to­sis. By ge­net­i­cal­ly en­gi­neer­ing these cells with CARs, we can specif­i­cal­ly di­rect them to tu­mor cells, such as ovar­i­an can­cer cells,” says co-founder Michael Klichin­sky, a PhD can­di­date in the de­part­ment of sys­tems phar­ma­col­o­gy and trans­la­tion­al ther­a­peu­tics at the Uni­ver­si­ty of Penn­syl­va­nia, in a pre­pared state­ment. “Our pre-clin­i­cal da­ta sup­port our hy­poth­e­sis and show tar­get­ed, se­lec­tive and ef­fec­tive killing of sol­id tu­mor cells by CAR­MA. In ad­di­tion, we ex­pect that CAR macrophages will prime a T cell im­mune re­sponse against the tu­mor.”

CAR­MA isn’t the on­ly new com­pa­ny to get start­ed out of Penn look­ing to play a big role in CAR-T’s sec­ond act. June al­so launched Tmu­ni­ty Ther­a­peu­tics, an­oth­er cell ther­a­py com­pa­ny, re­cruit­ing No­var­tis’ Us­man ‘Oz’ Azam to take the lead role at the com­pa­ny late last year.

Im­age: Saar Gill at AS­CO 2017 via ASH on YouTube

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.

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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.”

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Adeno-associated virus-1 illustration; the use of AAVs resurrected the gene therapy field, but companies are now testing the limits of a 20-year-old technology (File photo, Shutterstock)

Af­ter 3 deaths rock the field, gene ther­a­py re­searchers con­tem­plate AAV's fu­ture

Nicole Paulk was scrolling through her phone in bed early one morning in June when an email from a colleague jolted her awake. It was an article: Two patients in an Audentes gene therapy trial had died, grinding the study to a halt.

Paulk, who runs a gene therapy lab at the University of California, San Francisco, had planned to spend the day listening to talks at the American Association for Cancer Research annual meeting, which was taking place that week. Instead, she skipped the conference, canceled every work call on her calendar and began phoning colleagues across academia and industry, trying to figure out what happened and why. All the while, a single name hung in the back of her head.

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Pascal Soriot, AP

As­traZeneca CEO Pas­cal So­ri­ot sev­ers an un­usu­al board con­nec­tion, steer­ing clear of con­flicts while re­tain­ing im­por­tant al­liances

CSL Behring chief Paul Perreault scored an unusual coup last summer when he added AstraZeneca CEO Pascal Soriot to the board, via Zoom. It’s rare, to say the least, to see a Big Pharma CEO take any board post in an industry where interests can simultaneously connect and collide on multiple levels of operations.

The tie set the stage for an important manufacturing connection. The Australian pharma giant agreed to supply the country with 10s of millions of AstraZeneca’s Covid-19 vaccine, once it passes regulatory muster.

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Yanay Ofran (L) and Anat Binur (Ukko)

Leaps by Bay­er backs a pro­tein en­gi­neer­ing start­up tak­ing on Aim­mune — and Nestlé — in peanut al­ler­gy

Little capsules of peanut powder drove Nestlé’s $2.6 billion buyout of Aimmune. Now, with $40 million in new funding, a fledgling biotech is promising to bring a more sophisticated version of that protein therapy that can go much, much further.

Ukko’s goal is two-pronged — with the initial products spanning therapeutic and food — but it’s grounded in the same protein engineering platform, co-founder and CEO Anat Binur told Endpoints News.

As tar­get­ed ther­a­pies get ever more pre­cise, Deer­field un­veils $50M bet on an Har­vard pro­fes­sor's chem­istry in­sights

Behind the seemingly simple concept of targeted cancer therapies is the drug developer’s headache that the target is always changing. Each generation of kinase inhibitors may be ostensibly hitting the same oncogene, but in addition to blocking the wildtype oncogene, they must now also address the mutations that have developed along the way, spurring resistance to current drugs.

The more those target kinases evolve, too, the more they could resemble off-target kinases you don’t want to bind. So each iteration requires more selectivity — sometimes down to differences of a few atoms.

Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

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Anthony Fauci, NIAID director (AP Images)

As new Covid-19 task force gets un­der­way, threat looms of vac­cine, mon­o­clon­al an­ti­body-re­sis­tant vari­ants

Hours before President Biden’s Covid-19 team gave their first virtual press conference, the famed AIDS researcher David Ho delivered concerning news in a new pre-print: SARS-CoV-2 B.1.351, the variant that emerged in South Africa, is “markedly more resistant” to antibodies from convalescent plasma and vaccinated individuals.

The news for several monoclonal antibodies, including Eli Lilly’s bamlanivimab, was even worse: Their ability to neutralize was “completely or markedly abolished,” Ho wrote. Lilly’s antibody cocktail, which was just shown to dramatically reduce the risk of hospitalizations or death, also became far less potent.