In an­oth­er CRISPR first, Penn re­searchers dose US can­cer pa­tients with gene-edit­ed T cell ther­a­py

CRISPR has been test­ed in US pa­tients for the first time — but per­haps not in the man­ner you imag­ined.

The Uni­ver­si­ty of Penn­syl­va­nia has led the way dos­ing two pa­tients with re­lapsed can­cers — one with mul­ti­ple myelo­ma and one with sar­co­ma — with a T cell ther­a­py in which the T cell re­cep­tor and PD-1 pro­tein are edit­ed out.

Us­man “Oz” Azam

Fund­ing for the tri­al came part­ly from Tmu­ni­ty, a biotech co-found­ed by Penn’s CAR-T vi­sion­ary Carl June and helmed by No­var­tis vet Us­man “Oz” Azam. Park­er In­sti­tute for Can­cer Im­munother­a­py, an ear­ly in­vestor in Tmu­ni­ty, is al­so bankrolling the tri­al. A Penn spokesper­son con­firmed the news, which was first re­port­ed by NPR.

The ba­sic idea here is not un­like CAR-T, ex­cept with dif­fer­ent el­e­ments and tech­nolo­gies: Take a pa­tient’s T cells, en­gi­neer it to ex­press NY-ESO-1 TCR, while elim­i­nat­ing TCR and PD-1 orig­i­nal­ly on the sur­face us­ing CRISPR.

A group of UCLA and UCSF sci­en­tists backed by the Park­er In­sti­tute has been study­ing new tech­niques to get new genes in­to T cells — not just elim­i­nat­ing them — with CRISPR.

That’s not the most straight­for­ward way of ap­ply­ing the gene edit­ing tech, which has en­ticed oth­er drug de­vel­op­ers with the po­ten­tial to el­e­gant­ly fix ge­net­ic er­rors lead­ing to dis­ease. But it does speak to the ver­sa­til­i­ty of CRISPR, now a pop­u­lar­ized tool that’s spawned up­starts rang­ing from di­ag­nos­tics to tar­get­ed bac­te­ria erad­i­ca­tion.

Carl June

Nev­er­the­less, the trio of CRISPR pi­o­neers as­so­ci­at­ed — Ed­i­tas Med­i­cines, In­tel­lia Ther­a­peu­tics and CRISPR Ther­a­peu­tics — re­main the ones to watch for first-in-hu­man test­ing. In fact, just two months ago CRISPR Ther­a­peu­tics dosed the first pa­tient with its Ver­tex-part­nered be­ta tha­lassemia drug. It is al­so plan­ning to treat a sick­le cell dis­ease pa­tient with the same drug in mid-2019 for a sep­a­rate tri­al.

Of course, that’s as­sum­ing we’re talk­ing out­side of Chi­na, where in­fu­sions of CRISPR-edit­ed T cells in can­cer pa­tients have been tak­ing place for more than a year. In a stun­ner, Chi­nese sci­en­tist Jiankui He claimed the birth of ba­by twins who were ge­net­i­cal­ly mod­i­fied as fe­tus­es, stir­ring up wide­spread con­dem­na­tion and soul search­ing in the sci­en­tif­ic com­mu­ni­ty.

“2019 is the year when the train­ing wheels come off and the world gets to see what CRISPR can re­al­ly do for the world in the most pos­i­tive sense,” Fy­o­dor Urnov, a gene-edit­ing sci­en­tist at the Al­tius In­sti­tute for Bio­med­ical Sci­ences in Seat­tle and the Uni­ver­si­ty of Cal­i­for­nia, Berke­ley, told NPR.

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

Biohaven CEO Vlad Coric (Photo Credit: Andrew Venditti)

Pssst: That big Bio­haven Alzheimer's study? It was a bust. Even the sub­group analy­sis ex­ecs tout­ed was a flop

You know it’s bad when a biopharma player plucks out a subgroup analysis for a positive take — even though it was way off the statistical mark for success, like everything else.

So it was for Biohaven $BHVN on MLK Monday, as the biotech reported on the holiday that their Phase II/III Alzheimer’s study for troriluzole flunked both co-primary endpoints as well as a key biomarker analysis.

The drug — a revised version of the ALS drug riluzole designed to regulate glutamate — did not “statistically differentiate” from placebo on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11 (ADAS-cog) and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB).  The “hippocampal volume” assessment by MRI also failed to distinguish itself from placebo for all patients fitting the mild-to-moderate disease profile they had established for the study.

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CEO Stephen Yoder (Pieris)

Pieris fi­nal­ly vaults FDA hold on next-gen sol­id tu­mor hunter, clear­ing the path for mid-stage tri­al

Finally freed from the restraints of a partial FDA clinical hold on its lead HER2-positive solid tumor candidate, Pieris Pharmaceuticals is now racing toward Phase II.

The FDA slapped a partial hold on Pieris’ PRS-343 back in July, restricting the biotech from enrolling new patients in a Phase I trial. While Pieris was allowed to continue dosing patients who were already enrolled, the agency requested they conduct an additional “in-use and compatibility study” before recruiting any more.

News brief­ing: Ve­rastem CMO ex­its two weeks af­ter join­ing com­pa­ny; Ther­mo Fish­er inks $550M M&A deal

Two weeks after joining Verastem Oncology as chief medical officer, Frank Neumann is leaving the company for another job.

Neumann had joined Verastem after leaving bluebird bio, which surprisingly split into two companies last week, one in oncology and one in rare diseases. It’s not yet clear to where Neumann is headed next, but he noted in a statement that Verastem’s data and strategy were “truly exciting.”

FDA hits the brakes on His­to­gen's knee car­ti­lage ther­a­py, ask­ing for more in­fo on man­u­fac­tur­ing process

A month after filing the IND application for its human extracellular matrix designed to regenerate knee cartilage, Histogen has hit a roadblock.

The FDA on Tuesday verbally notified the San Diego-based biotech that it was placing a clinical hold on the planned Phase I/II clinical trial of HST-003 due to pending CMC information and additional questions needed to complete their review.

Histogen had planned to test the safety and efficacy of implanting hECM within microfracture interstices and related cartilage defects to regenerate that cartilage in conjunction with a microfracture procedure. The company said in a press release that it expects to receive written notice of the clinical hold from the FDA by Feb 12.

Andrew Allen, Gritstone CEO (Gritstone via website)

Grit­stone con­tin­ues Covid-19 push with deal to de­vel­op 'self-am­pli­fy­ing RNA' vac­cines, as shares con­tin­ue bal­loon­ing

Gritstone Oncology has had a big week, and it’s only Wednesday.

On Tuesday, the biotech revealed plans to start clinical testing of an experimental Covid-19 vaccine — in tandem with NIAID — that can also target other coronaviruses, with the goal of preventing future pandemics should SARS-CoV-2 prove difficult to cure with current vaccines. Then, on Wednesday morning, Gritstone licensed lipid nanoparticle technology from Genevant Sciences to develop what it’s calling “self-amplifying RNA vaccines” against Covid-19.

Hal Barron, GSK R&D chief (GSK via YouTube)

Glax­o­SmithK­line's $4B bis­pe­cif­ic can­cer drug al­liance with Mer­ck KGaA hit by big set­back with a PhI­II fail­ure on NSCLC

Close to 2 years ago, GSK’s R&D team eagerly agreed to pay up to $4 billion-plus to ally itself with Merck KGaA on a mid-stage bispecific called bintrafusp alfa, which intrigued them with the combination of a TGF-β trap with the anti-PD-L1 mechanism in one fusion protein.

But today the German pharma company says that their lead study on lung cancer was a bust, as independent monitors said there was no reason to believe that the experimental drug — targeting PD-L1/TGF-Beta — could beat Keytruda.

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Janet Woodcock and Joshua Sharfstein (AP, Images)

Poll: Should Joshua Sharf­stein or Janet Wood­cock lead the FDA from here?

It’s time for a new FDA commissioner to come on board, a rite of passage for Joe Biden’s administration that should help seal the new president’s rep on seeking out the experts to lead the government over the next 4 years.

As of now, the competition for the top job appears to have narrowed down to 2 people: The longtime CDER chief Janet Woodcock and Joshua Sharfstein, the former principal deputy at the FDA under Peggy Hamburg. Both were appointed by Barack Obama.

Bris­tol My­ers Squibb gets re­view date for Op­di­vo com­bo in gas­tric can­cer, look­ing to over­turn Keytru­da's 3-year lead

The past two months have been tough for Bristol Myers Squibb and its checkpoint inhibitor Opdivo after setbacks in lung and brain cancers. But in the battle against Merck’s Keytruda, any success matters — and now Bristol could be looking at a quick approval for Opdivo in an unmatched indication.

The FDA will launch a speedy review of a combination of Bristol Myers Squibb’s Opdivo and chemotherapy to treat first-line patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma, the drugmaker said Wednesday. The agency set an action date of May 25 for the application.