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Re­searchers in biotech, acad­e­mia and Big Phar­ma are of­fer­ing puz­zle pieces to crack CAR-T for sol­id tu­mors. Will they ever snap to­geth­er?

The idea seemed promising enough.

By the time a group of scientists reported an attempt to treat colon cancer with engineered T cells drawn from patients, expanded and armed with artificial surface proteins in 2010, the experimental therapy — known as CAR-T, short for chimeric antigen receptor transduced T cells — had turned from an eccentric therapeutic proposal to a somewhat viable approach being tested in the clinic. The target, HER2, was one of the most extensively studied targets in cancer, implicated in cancers of breast, bladder, ovary, pancreas, and more. A “next-generation” construct containing a fragment of a well-known antibody, deployed alongside additional tried and true tweaks, looked like a promising next step.

That’s not to mention the study was being conducted by Steve Rosenberg’s lab — the famed National Cancer Institute group that had produced some of the earliest data that convinced scientists of T cells’ ability to attack solid tumors.

Yet the trial took a shocking and tragic turn. Within 15 minutes of receiving the infusion, the first patient had serious trouble breathing. She was sent to the hospital, intubated, and died five days later.

“I think it shut every CAR-T cell therapy study down which targeted HER2 at the time,” recalled Stephen Gottschalk, who was working on a different HER2 program himself at Baylor College of Medicine. “We spent quite a lot of time with the FDA coming up with an approach that would allow us to do it safely.”

While CAR-Ts for hematological malignancies have largely sailed through those early safety scares — a group at Memorial Sloan Kettering had disclosed another death in a hematology trial that same year — and impressed the biopharma world with astonishing response rates, the same can’t be said about solid tumor efforts. Early clinical trials that didn’t turn up serious side effects also failed to demonstrate nearly the same level of efficacy seen in acute lymphoblastic leukemia and non-Hodgkin lymphoma.

Rather than giving up, both academic and industry researchers are doubling down, thanks in part to the big success in the hematologic space and the large market that awaits anyone who can finally unlock any kind of solid tumors with CAR-T.

The few skeptics haven’t stopped a torrent of venture dollars from propelling these efforts, most still preclinical, that promise to tear down the well-documented roadblocks now shielding many cancers from these potent killing cells. The question boils down to how you choose among them — and who will be the last ones standing.

Defining the challenge

Martin Pule remembers the early days when everything was harder in CAR-T.

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A new era of treat­ment: How bio­mark­ers are chang­ing the way we think about can­cer

AJ Patel was recovering from a complicated brain surgery when his oncologist burst into the hospital room yelling, “I’ve got some really great news for you!”

For two years, Patel had been going from doctor to doctor trying to diagnose his wheezing, only to be dealt the devastating news that he had stage IV lung cancer and only six months to live. And then they found the brain tumors.

“What are you talking about?” Patel asked. He had never seen an oncologist so happy.

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Mihael Polymeropoulos, Vanda Pharmaceuticals CEO

Phar­ma com­pa­ny con­tin­ues its FDA law­suit spree, this time af­ter agency de­nies fast-track des­ig­na­tion

Vanda Pharmaceuticals is making a name for itself, at least in terms of suing the FDA.

The DC-headquartered firm on Monday filed its latest suit against the agency, with the company raising concerns over the FDA’s failure to grant a fast track designation for Vanda’s potential chronic digestive disorder drug tradipitant, which is a neurokinin 1 receptor antagonist.

Specifically, Vanda said FDA’s “essential point” in its one-page denial letter on the designation pointed to “the lack of necessary safety data,” which was “inconsistent with the criteria for … Fast Track designation.”

Mod­er­na seeks to dis­miss Al­ny­lam suit over Covid-19 vac­cine com­po­nent, claim­ing wrong venue

RNAi therapeutics juggernaut Alnylam Pharmaceuticals made a splash in March when it sued and sought money from both Pfizer and Moderna regarding their use of Alnylam’s biodegradable lipids, which Alnylam claims have been integral to the way both companies’ mRNA-based Covid-19 vaccines work.

But now, Moderna lawyers are firing back, telling the same Delaware district court that Alnylam’s claims can only proceed against the US government in the Court of Federal Claims because of the way the company’s contract is set up with the US government. The US has spent almost $10 billion on Moderna’s Covid-19 vaccine so far.

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Cracks in the fa­cade: Is phar­ma's pan­dem­ic ‘feel good fac­tor’ wan­ing?

The discordant effects of the Covid-19 pandemic on pharma reputation continues. While the overall industry still retains a respectable halo from its Covid-19 quick response and leadership, a new patient group study reveals a different story emerging in the details.

On one hand, US patient advocacy groups rated the industry higher-than-ever overall. More than two-thirds (67%) of groups gave the industry a thumbs up for 2021, a whopping 10 percentage point increase over the year before, according to the PatientView annual study, now in its 9th year.

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Michael Corbo, Pfizer CDO of inflammation & immunology

UP­DAT­ED: Plan­ning ahead for crowd­ed ul­cer­a­tive col­i­tis mar­ket, Pfiz­er spells out PhI­II da­ta on $6.7B Are­na drug

Pfizer has laid out the detailed results behind its boast that etrasimod — the S1P receptor modulator at the center of its $6.7 billion buyout of Arena Pharma — is the winner of the class, potentially leapfrogging an earlier entrant from Bristol Myers Squibb.

Pivotal data from the ELEVATE program in ulcerative colitis — which consists of two Phase III trials, one lasting 52 weeks and the other just 12 weeks — illustrate an “encouraging balance of efficacy and safety,” according to Michael Corbo, chief development officer of inflammation & immunology at Pfizer. The company is presenting the results as a late breaker at Digestive Disease Week.

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Robert Califf (Michael Brochstein/Sipa USA via AP Images)

House Re­pub­li­cans at­tack Chi­na-on­ly da­ta in FDA sub­mis­sions, seek new in­ves­ti­ga­tion in­to re­search in­spec­tions

Three Republican representatives are calling on the FDA to take a closer look at the applications including only clinical data from China.

The letter to FDA commissioner Rob Califf late last week comes as the agency recently rejected Eli Lilly’s anti-PD-1 antibody, which attempted to bring China-only data but ran into a bruising adcomm that may crush the hopes of any other companies looking to bring cheaper follow-ons based only on Chinese data.

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David Mazzo, Caladrius Biosciences CEO

Blam­ing Covid dis­rup­tion, sup­ply short­ages, mi­cro­cap biotech hits the brakes on cell ther­a­py tri­al

More than two years into the Covid-19 pandemic, we’re not done seeing its disruption of biotech.

That’s according to Caladrius execs, who cited the pandemic as one reason for suspending its Phase IIb trial of a cell therapy as a treatment for coronary microvascular dysfunction (CMD). The company plans to go ahead on an interim analysis before deciding what to do with the program, which was built on a licensing deal with Shire in 2018.

Amid mon­key­pox fears, biotechs spring to ac­tion; Mod­er­na’s CFO trou­ble; Cuts, cuts every­where; Craft­ing the right pro­teins; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

It’s always a bittersweet moment saying goodbye, but as Josh Sullivan goes off to new adventures we are grateful for the way he’s built up the Endpoints Manufacturing section — which the rest of the team will now carry forward. If you’re not already, this may be a good time to sign up for your weekly dose of drug manufacturing news. Thank you for reading and wish you a restful weekend.

Co­pay coupons gone wrong, again: Pfiz­er pays al­most $300K to set­tle com­plaints in four states

Pfizer has agreed to pay $290,000 to settle allegations of questionable copay coupon practices in Arizona, Colorado, Kansas, and Vermont from 2014 to 2018.

While the company has not admitted any wrongdoing as part of the settlement, Pfizer has agreed to issue restitution checks to about 5,000 consumers.

A Pfizer spokesperson said the company has “enhanced its co-pay coupons to alleviate the concerns raised by states and agreed to a $30,000 payment to each.”