​One of the coolest ideas ever to treat cancer is being developed right in Charlestown

In In The News by Barbara Jacoby

By: Don Seiffert

From: bizjournals.com

A year ago, Ziopharm was scarcely known in the biotech world, having recently moved from New York City to Charlestown just a couple years after one of its drugs failed a late-stage trial.

Over the course of 2015, the company attracted worldwide notice for its early-stage treatments for cancer. In particular, attention has been on one unique approach, which amounts to a cancer drug with an on-off switch.

That technology has helped spur a 68 percent stock increase for the company over the course of the year, giving it a market value of $1.1 billion and making it among the top 10 biggest gainers among Massachusetts biotech companies in 2015.

In a recent call with investors, Ziopharm (Nasdaq: ZIOP) CEO Laurence Cooper confirmed that, based on the first seven patients in a Phase 1 trial of a cancer drug called Ad-RTS-IL-12, the on-off switch appears to work. So I recently spoke to Cooper about exactly how the drug is supposed to work, as well as when the company plans to provide more supporting data as to how well it helps patients.

Ad-RTS-IL-12 is among a currently-popular class of cancer drugs that work through the body’s immune system, called immunotherapies. But the drug’s specific mechanism of action is one not widely used. It spurs a protein called Interleukin 12 (IL-12), which Cooper likens to “calling all the troops out” in the body’s immune system. It essentially puts into action a bunch of other cytokines that all fight disease, he says.

Indeed, according to a February 2015 paper in Nature magazine IL-12 was said to have “emerged as one of the most potent cytokines in mediating antitumor activity in a variety of preclinical models.” The problem, the paper went on to say, is that “the robust antitumor response … has not yet been successfully translated into the clinics” and that the drug was “associated (with) toxic side effects.”

Cooper said the body is “very careful in how it uses IL-12,” since too much can result in a host of side effects. For years, biotech companies have tried to harness the power of IL-12, said Cooper, but they have failed due to their inability to control it once the initial “distress signal” is sent.

That’s where the on-off switch comes in. Ziopharm has a license from synthetic biology company Intrexon (NYSE: XON) to use a technology called the RheoSwitch, which essentially turns on and off a gene using a pill. Ziopharm is the only company licensed to use the technology in the field of oncology drugs, and the result is potentially a powerful way to tightly control the production of IL-12.

The way Ad-RTS-IL-12 works is, it’s injected directly into a patient’s tumor (Ziopharm is testing the drug in a severe form of brain cancer called glioblastoma as well as in breast cancer). The drug does nothing until activated by a pill, however. Cooper says the small molecules in the pill can get through the blood-brain barrier, overcoming one of the biggest problems with drugs for glioblastoma. The patient takes the pill daily unless he or she starts to exhibit side effects, in which case they can stop until those effects subside. In that way, Cooper hopes to succeed with Ziopharm’s drug where other biotechs have failed.

“Even at the lowest doses, we’re seeing we can turn on and off IL-12,” Cooper told me. That data, however, is from just seven patients (all with glioblastoma) and still needs to be confirmed in many more. Cooper says the next big update on the trial is planned for June 2016, at the annual meeting of the American Society of Clinical Oncology.

Ziopharm is developing other drugs as well, notably a type known as CAR-T, where it’s competing with companies including Lexington-based Agenus (Nasdaq: AGEN) as well as Santa Monica, California-based Kite Pharma (Nasdaq: KITE).

But it’s the company’s progress with the IL-12 drug which has arguably been behind the company’s rise from barely-known to widely-watched during 2015.

“Ziopharm started the year as a company with the potential to control IL-12,” said Cooper. “Now we’re ending the year with definite proof that we can control it.”