Off-the-shelf CAR-T from stem cells? An ear­ly look at UCLA tech — li­censed by Gilead

Less than two years af­ter the FDA first ap­proved No­var­tis and Gilead’s ground­break­ing au­tol­o­gous CAR-T treat­ments, the next rev­o­lu­tion in can­cer cell ther­a­py is al­ready rag­ing on as biotechs like Cel­lec­tis and Al­lo­gene be­gin test­ing prod­ucts made from healthy donor cells. UCLA sci­en­tists want to take the off-the-shelf ap­proach one step fur­ther by grow­ing a “vir­tu­al­ly un­lim­it­ed sup­ply” of T cells in the lab.

Amélie Mon­tel-Ha­gen

The tech­nique, which in­volves turn­ing pluripo­tent stem cells in­to ma­ture T cells, us­es be­spoke struc­tures called ar­ti­fi­cial thymic organoids — a sim­u­la­tion of the en­vi­ron­ment where blood stem cells de­vel­op in­to T cells in the body. The pub­li­ca­tion of the tech­nique in Cell Stem Cell back in Jan­u­ary was a boon for Gilead’s Kite, which li­censed the method for can­cer ther­a­py.

“Once we cre­ate ge­net­i­cal­ly edit­ed pluripo­tent stem cell lines that can pro­duce tu­mor-spe­cif­ic T cells in ar­ti­fi­cial thymic organoids, we can ex­pand those stem cell lines in­def­i­nite­ly,” said Amélie Mon­tel-Ha­gen, the study’s first co-au­thor.

A sec­tion of an ar­ti­fi­cial thymic organoid show­ing T cells (out­lined in red) cre­at­ed from hu­man em­bry­on­ic stem cells. UCLA

Click on the im­age to see the full-sized ver­sion

As­sum­ing these cells can be prop­er­ly tuned with gene edit­ing to go af­ter dif­fer­ent tu­mor types and pre­vent im­mune re­ac­tions from the pa­tient — a big as­sump­tion giv­en the ear­ly stage of re­search — it could rep­re­sent a big leap from cur­rent­ly avail­able CAR-T ther­a­pies that can on­ly be man­u­fac­tured one at the time, with the pa­tients’ own T cells, to vary­ing ef­fi­ca­cy.

Gay Crooks

It is, how­ev­er, un­clear how the man­u­fac­tur­ing ef­fi­cien­cy and ac­ces­si­bil­i­ty would com­pare with oth­er al­lo­gene­ic CAR-Ts in de­vel­op­ment. Al­lo­gene, which un­veiled some im­pres­sive com­plete re­sponse rates for its ther­a­py at ASH last year, says its process has po­ten­tial to treat around 100 pa­tients from a sin­gle man­u­fac­tur­ing run.

Still, the fact that the team starts with pluripo­tent stem cells is what makes the ap­proach ex­cit­ing, said Gay Crooks, di­rec­tor of UCLA’s Can­cer and Stem Cell Bi­ol­o­gy Pro­gram and se­nior au­thor of the study,

Their next step, the re­searchers say, will be to cre­ate T cells that pos­sess can­cer-fight­ing re­cep­tors but not mol­e­cules that cause re­jec­tion of the cells.

J&J gets a fresh OK for es­ke­t­a­mine, but is it re­al­ly the game-chang­er for de­pres­sion Trump keeps tweet­ing about?

Backed by an enthusiastic set of tweets from President Trump and a landmark OK for depression, J&J scooped up a new approval from the FDA for Spravato today. But this latest advance will likely bring fresh scrutiny to a drug that’s spurred some serious questions about the data, as well as the price.

First, the approval.

Regulators stamped their OK on the use of Spravato — developed as esketamine, a nasal spray version of the party drug Special K or ketamine — for patients suffering from major depressive disorder with acute suicidal ideation or behavior.

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FDA hands Mor­phoSys and In­cyte a quick OK on their po­ten­tial block­buster CAR-T al­ter­na­tive

Nearly three years after okaying the CAR-Ts Yescarta and Kymriah, the FDA has approved a new CD19 therapy.

MorphoSys’ Monjuvi, or tafasitamab-cxix, was cleared Friday for use in refractory diffuse large B-cell lymphoma (DBLCL). The approval sets up both MorphoSys and their commercial partner Incyte to compete with Gilead and Novartis in the ultra-competitive indication, where similar trial results and far easier delivery could allow them to cut a fair share of the market.

Covid-19 roundup: Eli Lil­ly retro­fits RVs for first-of-its-kind an­ti­body tri­al with NIH; Am­gen, Ab­b­Vie, Take­da team on a drug

Eli Lilly and the NIH are about to start a first-of-its-kind trial that researchers and developers have talked about for months as a way of providing temporary immunity to the most at-risk populations.

Lilly announced this morning that it will start a 2,400-person trial with the National Institute for Allergy and Infectious Diseases to test whether its experimental Covid-19 neutralizing antibody can prevent people in nursing homes and assisted living facilities from developing the disease. The idea, known as passive immunity, is that rather than waiting on a vaccine to induce people to develop antibodies, doctors can give them lab-grown antibodies. Ideally, those antibodies will either attack the new SARS-CoV-2 infection, if the patient has recently been exposed, or persist in the blood for several weeks and prevent infection or disease for that period.

So Covid-19 leader BioN­Tech has a can­cer vac­cine in de­vel­op­ment? Yes, and Re­gen­eron just jumped in for the PhII com­bo study

Before the coronavirus global emergency stole the R&D show in biopharma, the leaders in the race to develop new mRNA therapies had a big interest in determining if their tech could be used to create an effective cancer vaccine after all the first-gen tries had failed to impress. So perhaps it’s not surprising that an early cut of the data at frontrunner BioNTech went largely unnoticed.

Unless you were at Regeneron.

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Sanofi un­der for­mal in­ves­ti­ga­tion for De­pakine al­le­ga­tions; Beam li­cens­es CAR-T tech from Ox­ford Bio­med­ica

Sanofi is facing a formal investigation on manslaughter charges, due to accusations that its epilepsy drug Depakine caused birth malfunctions and slow neurological development when taken during pregnancy.

The French pharma was formally charged in February, years after evidence surfaced that the drug, sodium valproate, posed neurodevelopmental risks. Sodium valproate first hit the market in 1967 for the treatment of epilepsy and bipolar disorder, and is currently prescribed in more than 100 countries.

Rich Heyman (ARCH)

Rich Hey­man joins PMV Phar­ma, a p53 biotech, as it adds $70 mil­lion in Se­ries D

Less than a year after pulling in an impressive $62 million Series C round, PMV Pharma is back at it again.

The Cranbury, NJ-based biotech announced Monday an additional $70 million in Series D financing as it seeks to develop cancer therapies targeting p53 mutations. Additionally, PMV also introduced longtime biotech entrepreneur Rich Heyman as chairman of the board of directors.

“This financing provides PMV Pharma with the resources to expand our pipeline and to potentially advance multiple p53 therapies into the clinic,” said PMV president and CEO David Mack in a statement.

Days af­ter seal­ing Sanofi pact, Kymera beats a path to the Nas­daq with $100M IPO pitch

Back in March, when Kymera Therapeutics closed $102 million in Series C funding led by Biotechnology Value Fund and Redmile Group, CEO Nello Mainolfi noted the protein degradation player was “at the cusp of transitioning” into a fully integrated R&D company. Five months and a major Sanofi pact later, he’s back asking for another little push to get there.

Kymera has penciled in $100 million in its first IPO pitch — although given the public market’s seemingly insatiable appetite for biotechs these days the final figure is anyone’s guess.

CymaBay flash­es pos­i­tive re­sults from the tri­al they have to re­launch

Two weeks after the FDA lifted its clinical hold on their lead drug, CymaBay said it showed positive results in an aborted Phase III trial.

The drug, a small molecule known as seladelpar, had been in development for three different liver conditions before an independent review of a NASH study last year showed that it might actually be damaging patient’s liver cells. The FDA slapped a clinical hold across all three trials, only lifting it last month when an FDA review determined that the drug hadn’t caused liver damage.

Sev­en plucky di­ag­nos­tics com­pa­nies win a $249M round of con­tracts af­ter sur­viv­ing NI­H's Covid-19 'Shark Tank' com­pe­ti­tion

As US Covid-19 deaths creep past 150,000 and officials stress the importance of contact tracing, the NIH’s Rapid Acceleration of Diagnostics (RADx) program has inked contracts totaling $248.7 million to expand testing capabilities.

The seven contracts, which were chosen “Shark Tank”-style from a pool of 100 proposals, are part of an effort to bump daily testing capacity to 2% of the country’s population by late summer or fall. That would be about 6 million people per day, compared to the current 520,000 to 823,000 tests being administered daily.