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Off-the-shelf CAR-T, a Tagrisso rival and the next breast cancer drugs: a look ahead at ASCO

On Wednesday evening, cancer doctors and researchers got an early peek at the clinical trial results set to be presented next month at the American Society of Clinical Oncology’s annual meeting.

The release of study abstracts a few weeks before the meeting often sets the stage for what will be discussed and debated at the conference. For investors in the drugmakers developing new cancer drugs, the abstract “drop” can swing stock prices widely in either direction.

This year, there were a number of abstracts that stood out, including important results for a new Bristol Myers Squibb immunotherapy that BioPharma Dive covered separately. Allogene Therapeutics offered the latest look at the durability of “off-the-shelf” cell therapy for cancer, while EQRx released data that could determine whether its unorthodox plan to undercut top-selling medicines succeeds.

Sanofi and Lilly, meanwhile, will have early data for breast cancer drugs they hope could become backbone therapies. Here’s a detailed look at each:

An off-the-shelf cell therapy remains competitive

Allogene has been at the forefront of a race to determine whether off-the-shelf, or “allogeneic,” cancer cell therapies can be just as effective as their more logistically complex, “autologous” CAR-T counterparts. Doing so could help substantially broaden the reach of CAR-T treatments, which, while powerfully effective, take weeks to produce and require lengthy hospital stays.

Early results from Allogene’s lymphoma treatment, ALLO-501, over the past year has shown response rates generally in line with what’s been reported for Gilead’s Yescarta and Novartis’s Kymriah. Importantly, no patients experienced graft-versus-host disease, a potentially deadly immune reaction and a key worry with off-the-shelf treatments using genetically engineered cells from donors. Neurological and immune side effects typically associated with CAR-T weren’t any more common with ALLO-501.

“There’s no indication that the allogeneic approach creates more safety issues,” said CEO David Chang, in an interview.

The major question with allogeneic treatment is whether patients will respond as long as they would to autologous CAR-T. That hasn’t been fully answered yet, but new results Allogene disclosed Wednesday pointed to encouraging signs: 4 of 12 large B-cell lymphoma patients with complete responses, or no trace of cancer, for at least six months. One of them was cancer free 15 months after treatment.

The numbers looked worse in follicular lymphoma patients (4 of 17), putting the overall six-month complete response rate across the two groups just below a 30% bar several analysts have established. Chang cautioned, however, that the denominator is small and expects a better outcome with bigger patient numbers.

The results are “right on par with what the autologous CAR-T therapies have shown,” Chang said, adding that a CAR-T response lasting six months is often an indication the effects will hold up much longer. Treatments like Yescarta, Kymriah and Bristol Myers Squibb’s Breyanzi had six-month complete response rates between 29% and 40% in the pivotal trials that led to their approvals.

“We think it’s highly notable that the vast majority of patients who achieved CR beyond 6-months haven’t progressed,” wrote Stifel analyst Benjamin Burnett. “That, in our opinion, feels very much like auto-CAR-T.”

Allogene will begin a potentially pivotal Phase 2 trial of ALLO-501a, a similar product to ALLO-501, in LBCL later this year, Chang said. Shares initially climbed by as much as 11% before falling back to trade down 5%.

 A “coming out party” for an unusual biotech

Startup EQRx turned heads a few years ago when it launched with $200 million and the unusual goal of developing lower-cost alternatives to branded medicines. The biotech’s plan is to either acquire or make drugs that work the same way as proven medicines, prove they are as good or better and sell them at a fraction of the cost.

EQRx has since amassed a pipeline of drugs that mimic some of the industry’s top-sellers. Among them are a cancer immunotherapy in the mold of Merck & Co’s Keytruda and Bristol Myers Squibb’s Opdivo, and a so-called CDK 4/6 inhibitor, a type of breast cancer drug similar to Pfizer’s Ibrance and Eli Lilly’s Verzenio.

This year’s ASCO marks the first indication that the biotech’s plan might work. Ahead of the meeting, EQRx disclosed results showing a lung cancer drug it acquired from China’s Hansoh Pharmaceutical Group last year bested Pfizer’s Iressa in a Phase 3 trial in patients whose tumors have a mutation called EGFR. Median progression-free survival — a measure of how long tumors are held in check — was 19.9 months for patients on EQRx’s aumolertinib versus 9.9 months for Iressa. Instances of diarrhea or rash, two common side effects of drugs in EQRx’s drug’s class, were “clearly less severe and frequent” than Iressa, said EQRx physician-in-chief Vincent Miller.

Iressa, however, isn’t EQRx’s target. It’s AstraZeneca’s Tagrisso, which in recent years has become a multi-billion-dollar product with a U.S. list price of almost $180,000. Hansoh’s trial began in 2018, before Tagrisso was available in China, so the two drugs weren’t tested against one another. But EQRx “would consider” such a trial in the future, Miller says, along with tests in earlier lung cancer settings in which Tagrisso has excelled.

Though it’s difficult to compare one trial to another, EQRx’s results were similar to what Tagrisso produced in the Phase 3 FLAURA study that led to its approval in first-line lung cancer, with an “at least numerically favorable” side effect profile to Tagrisso, Miller said.

The results set up EQRx to submit approval filings in the U.S. and Europe for the treatment, which is already marketed in China. Assuming approval, it will be priced “significantly lower” than the competition, said company president Melanie Nallicheri, without providing specifics.

“We’ve said jokingly that this is our coming out party,” she said. “It really shows what we can do.”

Hints of promise for a second generation of breast cancer drugs

In about two-thirds of breast cancer cases, tumor cells express proteins that latch onto the hormones estrogen or progesterone, fueling their growth. For decades, drugs that either block those proteins or lower hormone levels in the body have been standard treatments.

One such drug, called fulvestrant and approved in 2002, works uniquely by both blocking and degrading hormone receptor proteins. It’s commonly used, although it has a number of limitations.

Drugmakers have been working for years to develop safer and more effective therapies that work similarly as fulvestrant, all part of a drug class dubbed selective estrogen receptor degraders, or SERDs. Several previous efforts failed, but recent progress could put SERDs back in the spotlight.

At ASCO next month, Sanofi and Eli Lilly will present early data for their candidates. Sanofi’s, in particular, is crucial to the French pharma’s ambitions in oncology drug development.

Data from a Phase 1 study abstract released ahead of the meeting show some promise. Treatment with Sanofi’s drug, called amcenestrant, and Pfizer’s Ibrance, shrank tumors in about a third of treated patients. About three-quarters had no disease progression.

Importantly, there were no signs of cardiac or eye side effects, two particular areas of concern with SERDs.

Sanofi is waiting on data from a larger clinical trial testing amcenestrant against doctor’s choice of therapy in metastatic estrogen receptor-positive breast cancer. But results are now due a bit later than expected: the company expects data in the second half of this year, rather than this quarter.

For Lilly’s drug, the data released Wednesday are limited to safety findings. Updated results will come at ASCO itself.