Stan­ford tri­al points to a new CAR-T drug, spot­light­ing a fresh tar­get for next-gen cell ther­a­pies

CAR-T re­searchers have had years to study CD19 pro­tein mol­e­cules as a tar­get in their suc­cess­ful leukemia stud­ies. But a small, ex­plorato­ry study at Stan­ford un­der­scores that there’s sub­stan­tial promise in ex­pand­ing their scope to in­clude CD22, of­fer­ing a new route to fol­low for pa­tients who re­lapse — or nev­er re­spond — af­ter be­ing treat­ed with the first round of cell ther­a­pies now hit­ting the mar­ket.

Crys­tal Mack­all

The re­search team re­cruit­ed 15 pa­tients for this tri­al who had ei­ther re­lapsed or nev­er re­spond­ed to CD19-tar­get­ed CAR-T ther­a­py, which in­volves ex­tract­ing a pop­u­la­tion of T cells from pa­tients and adapt­ing them with a chimeric anti­gen re­cep­tor so they would tar­get a pro­tein com­mon­ly found on the sur­face of leukemia cells. Ten of them had re­lapsed, with their can­cer cells no longer ex­press­ing CD19.

Af­ter step­ping up the dose from the first round, the re­searchers achieved re­mis­sion in 11 of the 15 pa­tients — a re­mark­able 73%. The re­mis­sions last­ed a me­di­an of 6 months with one pa­tient in re­mis­sion at 21 months, with signs that the can­cer cells were able to mu­tate to stop ex­press­ing CD22 and es­cape the ther­a­peu­tic as­sault.

“The take-home mes­sage is that we’ve found an­oth­er CAR T-cell ther­a­py that dis­plays high-lev­el ac­tiv­i­ty in this Phase I tri­al,” said Stan­ford’s Crys­tal Mack­all, who led the study. “But the re­lapse rate was al­so high. So this forces the field to get even more so­phis­ti­cat­ed. How much of a tar­get is need­ed for suc­cess­ful, long-last­ing treat­ment? What hap­pens if we tar­get both CD19 and CD22 si­mul­ta­ne­ous­ly?”

Stan­ford’s team re­port­ed progress with CD22 four days af­ter in­ves­ti­ga­tors at Seat­tle Chil­dren’s launched a com­bi­na­tion CAR-T tri­al us­ing a new cell ther­a­py that could si­mul­ta­ne­ous­ly at­tack CD19 and CD22, look­ing for a more po­tent and con­sis­tent strat­e­gy for acute lym­phoblas­tic leukemia that could con­ceiv­ably cut the re­lapse rate in half, while al­so tak­ing an­oth­er step down a path to­ward us­ing CAR-T in sol­id tu­mors — one of the Holy Grails that has emerged in the field.

(Ed­i­tor’s note: Af­ter we pub­lished this sto­ry, one of our read­ers point­ed out that Au­to­lus al­so just start­ed a PhI/II study us­ing a CD19/CD22 CAR-T.)

The small tri­al at Stan­ford is sig­nif­i­cant for a va­ri­ety of rea­sons. While No­var­tis and Gilead/Kite have be­gun the process of field­ing the first new ther­a­pies, the em­pha­sis in re­search cir­cles has shift­ed to cre­at­ing a new, safer gen­er­a­tion of CAR-Ts that can be far more durable. Al­so, Mack­all told The New York Times, it’s im­por­tant to un­der­stand that CD19, for all its re­mark­able ef­fect in of­fer­ing a bea­con for cell ther­a­pies, is “not some kind of uni­corn.”

More tar­gets ex­ist that will work here, she says. And that’s where re­searchers will turn next.

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.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,200+ biopharma pros reading Endpoints daily — and it's free.

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.

Covid-19 claims an­oth­er PDU­FA vic­tim as Glax­o­SmithK­line push­es back planned PD-1 roll­out

Bristol Myers Squibb isn’t the only pharma giant that’s been standing in the FDA’s waiting line for site inspections.

GlaxoSmithKline is telling us today that their H2 2020 PDUFA deadline for the PD-1 drug dostarlimab — picked up in its Tesaro buyout — was pushed back due to a delay in the manufacturing site inspection needed for a regulatory decision. And that is forcing the company to revise its timeline.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,200+ biopharma pros reading Endpoints daily — and it's free.