Eureka Thera’s CAR-T treatment shrinks liver cancer in small study. What’s the big deal? Just ask Sloan-Kettering and Germany’s Boehringer.

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The News:

Eureka Therapeutics Inc., a closely held biotechnology company, said that liver cancer patients getting its CAR-T therapy responded to the treatment, one of the first times the immune-system modifying treatments have been shown to work in solid tumors, Bloomberg reports.

Three of the six liver cancer patients in the Chinese study had their tumors shrink after receiving the treatment, and one patient, a 52-year-old man, had no signs of cancer after six months. The patients–all of whom previously failed multiple drugs–also showed no signs of cytokine release syndrome, a potentially harmful side effect caused by the immune system’s powerful attack on malignant cells following treatment.

“The results were extremely surprising,” said Chang Liu, a physician at Xi’an Jiaotong University in China and the primary investigator in the Eureka study. “This is a breakthrough in an area where there was previously no known treatment. To be more dramatic, we can say it’s created a miracle.”

The research results were presented at the CAR-TCR Summit in Boston September 5-7, 2018, a medical meeting focused on the new therapies that modify immune cells to attack cancer.

While US regulators have approved CAR-T products from Novartis AG and Gilead Sciences Inc. to treat some blood cancers, solid tumors like those found in the liver and breast have seen less success in experimental tests.

Current CAR-T therapies target proteins found on the outside of cells and destroy some healthy cells as well as the cancer cells. While Eureka’s approach still requires engineering a patient’s immune system T-cells, its technology targets tumors based on specific markers from the malignant cells, making the therapy more precise.

Three of the patients in the study died. Eureka and Liu said the deaths were unrelated to the treatment.

Emeryville, CA-based Eureka plans to begin an early-stage study in the US in 2019.

Steve’s Take:

Now we’re getting somewhere really exciting in the realm of cancer “cures.” And it’s coming from a little northern California biotech with the silly name its founders and employees hope doesn’t come back to bite them.

A new chimeric antigen receptor (CAR) T-cell receptor from Eureka Therapeutics is credited with a surprising impact in a small study of advanced liver cancer, raising the first glimmer of hope for solid tumors, says Endpoints.

In a proof-of-concept study involving six patients with hepatocellular carcinoma–the most prevalent form of liver cancer–researchers reported that one patient had a complete response, which was maintained at the seven-month checkup. Two others saw their tumors shrink.

These, the biotech emphasizes, are patients who have failed multiple prior treatments.

Eureka added that none of the patients experienced cytokine release syndrome or drug-related neurotoxicity–well-known safety concerns that have limited the use of T-cell therapies.

The first CAR-Ts on the market from Gilead/Kite and Novartis have demonstrated some amazing results for blood cancers, but solid tumors have represented a high hurdle for these new drugs. Clearing it–safely–would open up a huge market.

“We are encouraged by the safety profile and the potential efficacy of ET140202 for AFP-positive liver cancer,” said Cheng Liu, Eureka’s president and CEO. “Combining T-cell therapy with a TCR-mimic antibody to target intracellular antigens is a novel approach and can potentially represent a powerful way to treat solid tumors, and in particular, liver cancer, an area of significant unmet medical need.”

The treatment, dubbed ET140202, works by targeting a liver cancer marker called alpha-fetoprotein, or AFP.

In 2019, the company plans to launch a multicenter Phase 1 trial for ET140202, in the US, where it’s also testing its lead program focused on CD19+ non-Hodgkin lymphoma.

Left out of the news reports of the company’s presentation in Boston last week were 2 crucial pieces of earlier news.

First, back in July, Eureka announced that Boehringer Ingelheim GmbH had elected to exercise an option for the exclusive license of novel human TCR-mimicking (TCRm) antibodies against an undisclosed target to be used for the potential development and commercialization of therapies for cancer patients. The licensed TCRm antibodies were developed under a research collaboration and license agreement between Eureka and Boehringer established in 2015.

It’s not a stretch to suggest the “undisclosed target” was liver cancer.

Eureka will receive an undisclosed option payment from Boehringer and is eligible to receive development, regulatory and commercial milestone payments, as well as royalties on net sales, related to antibodies directed at the optioned target, the company said.

Then, in August, Eureka and Memorial Sloan Kettering (MSK) announced they had pioneered a new CAR-T technology that caught almost all observers off guard. A paper describing the approach was published in the journal Nature Biotechnology on August 17, according to Contract Pharma.

Eureka and MSK said they had built a new model of CAR-T cells, ones with powerful “armor” that allow them to fight solid tumors. A paper describing the approach was published in the journal Nature Biotechnology.

In addition, because the checkpoint drugs were released directly into the tumor, they activated nearby T cells, creating a helpful bystander effect. The companies say the approach can be thought of as providing a new platform for CAR therapy.

“We can build CAR-T cells to secrete a variety of different molecules, tailored to the needs of the patient. It’s not just limited to this one drug,” said Renier Brentjens, director of the Cellular Therapeutics Center at MSK and one of the pioneers of CAR therapy.

Bottom Line:

If ever there were ripe conditions for either an IPO or an outright sale at an enormous premium, Eureka Therapeutics fits the bill for both. Why?

Well, the study results speak for themselves. They’re wildly positive. Sure, there’s lots of work still to do to prove they’re really onto something solid, clinically.

Steve's Take: If ever there were ripe conditions for either an #IPO or an outright sale at an enormous premium, @EurekaThera fits the bill for both. Click To Tweet

But companies like Boehringer have been seeing something solid enough in Eureka’s science to exercise its option to join the party, clinically that is, and share in what undoubtedly will be a blockbuster profit stream since their treatment would likely be the first approved for solid tumors.

Of course, there’s plenty of risk that everything goes thud, as is usually the case in new I/O treatment crusades. But you won’t find organizations with the stature of Memorial Sloan Kettering cozying up to such a small, silly-sounding biotech like Eureka if the science evolving there for over a decade isn’t pretty darn solid.

I’ll keep my eye on Eureka, and we can all watch from the safety of the sidelines until the 2019 US study gets off the ground and we start seeing more data. Stay tuned.


On September 13, 2018, Endpoints reported that Boehringer Ingelheim had bought the oncolytics virus biotech ViraTherapeutics GmbH in a $244 million deal.

Boehringer 3 years ago decided it would take an active role in fostering the tiny Austrian biotech. The German company’s venture arm invested in the fledgling’s biotech’s tiny $4 million A round in the summer of 2015. BI execs came back with a $230 million “discovery” deal–building in a buyout option–and then added a second program. Now they’re going all-in, buying the company.

What’s significant here is that Eureka’s I/O technology could fit quite nicely with ViraTherapeutics’ oncolytic viruses, which are the Trojan horse of immuno-oncology. The viruses are designed to infect cancer cells, invading the disease, and then exploding them, which subsequently signals the immune system to mount an attack on the survivors. There’s a clear clinical track record showing how they work.

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