September 08, 2015

New Appoach targets Cancer Stem Cells and uses tens of thousands of animal models

Stemcentrx, has raised $500 million and is valued at $3 billion, people familiar with its finances say, a nearly unprecedented value for a company with no revenue, facing the usual R and D obstacles, and that almost no one has heard of.

Silicon Valley is used to “unicorns,” those private, usually profitless, and fast-growing tech companies worth a billion dollars or more, like Snapchat, Square, and Uber. Now the same phenomenon is spreading to biotech, where investors are throwing money at companies that promise to beat the historically low odds of drug success.

The company is unusual because it’s betting on a scientific idea that’s not universally accepted—that cancer is caused not by any cell that goes rogue, but by rare and powerful cancer stem cells.

Stemcentrx’s contrarian premise—that stem cells can be bad, not good—has drawn some impressive backers, including Sequoia Capital, Elon Musk, and most notably Founders Fund, the investment firm led by Peter Thiel, the Midas-touch investor who discovered Facebook.

Thiel says his fund has invested $200 million into Stemcentrx. It is the fund’s largest investment ever in a single company, he says, surpassing well-known names like SpaceX, Spotify, and Palantir. It’s also two to three times the total Thiel has invested in about 25 other biotechnology firms

Cancer Stem Cells: the roots of a tumor

Cancer stem cells initiate and perpetuate tumor growth, and are more resistant to chemotherapy and radiation therapies. Cancer stem cells are the tumor cells that metastasize, causing cancer to spread throughout the body.

Smart targeting

Stemcentrx therapies are engineered to target cancer stem cells, subsequently delivering a potent drug that can kill them. We believe that targeting and eliminating cancer stem cells will enable long-term patient survival.

Disease-specific cancer drugs

Cancers occur in many forms and our data indicate each cancer subtype should be targeted specifically. Stemcentrx has discovered and is developing drugs for a number of cancer subtypes. We are also developing companion diagnostic tests that can be used to identify patients most likely to benefit from those drugs.

Stemcentrx has five investigational drugs in human clinical trials. As single agents, three have generated objective clinical responses in patients with small cell lung cancer, triple-negative breast cancer, ovarian cancer, and peritoneal cancer, and two have recently begun phase I clinical trials. Beyond these five clinical programs, we have a pipeline of additional novel targets to address other major cancer types.

Laboratory Investigation - Patient-derived xenografts, the cancer stem cell paradigm, and cancer pathobiology in the 21st century

Science Translational Medicine - A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo

At the Stemcentrx labs, I saw technicians skinning dark balls of lung tumors the size of lychee nuts, then dicing them with a razor blade. Researchers run the cells through sorting machines, using chemical markers to separate them into different types. Dylla says the company grafts tumor cells into more than 150 mice a day.

The aim isn’t only to find a specific cell that can generate a cancer, but also a unique molecular marker that identifies it. One discovery Stemcentrx says it made was to find a protein, called DLL3, that appears on what it thinks are stem cells responsible for small cell lung cancer. The drug they created to kill these cells is a chemical toxin linked to an antibody that attaches to this protein, lock and key style.

At Stemcentrx, tumors from 600 different people and from a dozen types of cancer grow inside its 18000 mice. Dylla’s conviction is that if its drugs can cure the animals, the chances are higher they will help people. For Stemcentrx to justify its lofty valuation it probably needs a success rate about three times the biotech average.

What’s more, the company is betting on a paradigm that’s still hotly contested. The stem cell theory implies cancer is organized like an organ, say your liver, whose stem cells constantly make new specialized cells, like after you’ve nuked a few during a night of bar hopping. In the cancer stem cell scenario, a tumor would work in a similar way. So if you destroyed the relatively rare stem cells, the cancer couldn’t grow back.

SOURCES - Stemcentrx, Technology Review

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