With CAR-T mar­ket­ing loom­ing, ear­ly study high­lights po­ten­tial of TCR en­gi­neer­ing

With the first gen­er­a­tion of CAR-Ts like­ly head­ed to a near-term ap­proval for blood can­cers, the clin­i­cal work on new adop­tive TCR-en­gi­neered cell ther­a­pies that can work in sol­id tu­mors is un­der­way.

Steven Rosen­berg

This week, a re­search team led by the NIH’s Steven Rosen­berg — whose work has been used as a ba­sis of Kite Phar­ma’s pi­o­neer­ing CAR-T — rolled out ear­ly proof-of-con­cept da­ta from a small hu­man study us­ing a CD4+ T cell adapt­ed with a T cell re­cep­tor that ze­roes in on MAGEA3, or melanoma-as­so­ci­at­ed anti­gen A3.

Prepped with a lym­phode­ple­tion reg­i­men and in­fused with a pu­ri­fied batch of cell ther­a­py, the re­searchers treat­ed 17 pa­tients. One pa­tient ex­pe­ri­enced a com­plete re­sponse which is on­go­ing at 29 months. Of 9 pa­tients treat­ed at the high­est dose, three suf­fer­ing from esophageal can­cer, urothe­lial can­cer, and os­teosar­co­ma had par­tial re­spons­es.

Rosen­berg and his team con­clud­ed that the PoC da­ta was en­cour­ag­ing for this ap­proach, a point which Kite ex­ec­u­tives were quick to en­dorse.

KITE-718 is al­ready in the clin­ic, and it’s been de­signed along the same TCR en­gi­neer­ing that Rosen­berg was try­ing out at the NIH.

There are num­ber of com­pa­nies work­ing on TCR ther­a­pies, in­clud­ing Adap­ti­m­mune $ADAP, which is close­ly al­lied with Glax­o­SmithK­line as the phar­ma gi­ant looks at be­com­ing much more ac­tive in the on­col­o­gy field. While CAR-Ts have had a big im­pact on liq­uid can­cers, sol­id tu­mors have re­mained a chal­lenge, in­spir­ing these next-gen ap­proach­es.

There are some key con­cerns about off-tar­get tox­i­c­i­ty here, un­der­scored by two deaths four years ago in one of Adap­ti­m­mune’s TCR stud­ies aimed at MAGEA3. They both died of heart fail­ure, which was sub­se­quent­ly tied to an un­ex­pect­ed im­pact on car­diac mus­cle cells.

There were no signs of such tox­i­c­i­ty in the NIH study, but you can bet that af­ter the big safe­ty is­sues that af­flict­ed ear­ly CAR-T stud­ies, it will be a ma­jor fo­cus for all con­cerned.

“We are very ex­cit­ed by the re­sults of this study con­duct­ed by our col­lab­o­ra­tors at the NCI, demon­strat­ing the po­ten­tial of TCR en­gi­neered T-cell ther­a­py in com­mon sol­id tu­mors,” said David Chang, Kite’s CMO. “The KITE-718 pro­gram is built up­on this proof of con­cept study and in­cor­po­rates Kite’s next gen­er­a­tion T-cell man­u­fac­tur­ing tech­nol­o­gy that is de­signed to en­hance cell ex­pan­sion and per­sis­tence. The find­ings from the NCI study will help in­form us as we ad­vance KITE-718 for the treat­ment of metasta­t­ic sol­id can­cers, for which there is a great un­met med­ical need.”

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.

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.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,700+ biopharma pros reading Endpoints daily — and it's free.

Jackie Fouse, Agios CEO

Agios scores its sec­ond pos­i­tive round of da­ta for its lead pipeline drug — but that won't an­swer the stub­born ques­tions that sur­round this pro­gram

Agios $AGIO bet the farm on its PKR activator drug mitapivat when it recently decided to sell off its pioneering cancer drug Tibsovo and go back to being a development-stage company — for what CEO Jackie Fouse hoped would be a short stretch before they got back into commercialization.

On Tuesday evening, the bellwether biotech flashed more positive topline data — this time from a small group of patients in a single-arm study. And the executive team plans to package this with its earlier positive results from a controlled study to make its case for a quick OK.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,700+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints Premium

Premium subscription required

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

George Yancopoulos (L) and Len Schleifer (Regeneron)

Re­gen­eron touts pos­i­tive pre­lim­i­nary im­pact of its Covid an­ti­body cock­tail, pre­vent­ing symp­to­matic in­fec­tions in high-risk group

Regeneron flipped its cards on an interim analysis of the data being collected for its Covid-19 antibody cocktail used as a safeguard against exposure to the virus. And the results are distinctly positive.

The big biotech reported Tuesday morning that their casirivimab and imdevimab combo prevented any symptomatic infections from occurring in a group of 186 people exposed to the virus through a family connection, while the placebo arm saw 8 of 223 people experience symptomatic infection. Symptomatic combined with asymptomatic infections occurred in 23 people among the 223 placebo patients compared to 10 of the 186 subjects in the cocktail arm.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,700+ biopharma pros reading Endpoints daily — and it's free.

Hal Barron, GSK via YouTube

What does $29B buy you in Big Phar­ma? In Glax­o­SmithK­line’s case, a whole lot of un­com­fort­able ques­tions about the pipeline

Talk about your bad timing.

A little over a week ago, GSK R&D chief Hal Barron marked his third anniversary at the research helm by taking a turn at the virtual podium during JP Morgan to make the case that he and his team had built a valuable late-stage pipeline capable of churning out more than 10 blockbusters in the next 5 years.

And then, just days later, one of the cancer drugs he bet big on as a top prospect — bintrafusp, partnered with Merck KGaA — failed its first pivotal test in non-small cell lung cancer.

Endpoints Premium

Premium subscription required

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

Vir's CMO says he's sur­prised that a low dose of their he­pati­tis B drug ap­pears promis­ing in ear­ly slice of da­ta — shares soar

Initial topline data from a Phase I study of a new therapeutic for chronic hepatitis B virus was so promising that it surprised even the CMO of the company that produces it.

Vir Biotechnology on Tuesday announced that its VIR-3434 molecule reduced the level of virus surface antigens present in a blinded patient cohort after eight days of the trial with just a single 6 mg dose. Six of the eight patients in the cohort were given the molecule, and the other two a placebo—all six who received the molecule saw a mean antigen reduction of 1.3 log10 IU/mL, Vir said.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 98,700+ biopharma pros reading Endpoints daily — and it's free.

David Marek, Myovant

My­ovant beefs up da­ta pack­age in NDA #3, boost­ing its case for longterm dos­ing of Pfiz­er-part­nered re­l­u­golix

When Pfizer handed over $650 million in cash to partner on Myovant’s relugolix, the pharma giant made clear that the deal — valued at $4.2 billion total — was just as much about the approved indication of prostate cancer as the two women’s health conditions the drug could treat.

A month later, the two companies are offering another glimpse of the therapy’s longterm potential in endometriosis.

Look­ing to win over some skep­ti­cal an­a­lysts, Rhythm beats the drum on in­ter­im da­ta in PhII bas­ket study for ad­di­tion­al in­di­ca­tions

Rhythm Pharmaceuticals has been working toward expanding the FDA approval they received just two months ago for three rare genetic disorders that result in obesity. In December, their Phase III cut of data saw mixed reactions from analysts, but new interim results released Tuesday may provide more excitement.

In an ongoing Phase II study for setmelanotide across individuals with one of three distinct rare genetic diseases of obesity, 65 patients had reached the Dec. 17 cutoff date for evaluation. Among patients who met the primary endpoint of at least 5% weight loss over three months, Rhythm saw an average reduction of no less than 7.1% in any of the groups.