In Turnaround Saga, Ignyta Nears Crucial Phase in Cancer Drug Trial

Xconomy San Diego — 

Biotech CEO Jonathan Lim co-founded Ignyta in 2011 to commercialize a new approach to diagnosing and treating rheumatoid arthritis, based on discoveries that showed how changes in methyl group molecules associated with the human genome could change the way genes function.

Instead, Lim may end up showing how to breathe new life into a life sciences company that was flat-lining, at least in terms of developing new technology.

As a tool for diagnosing rheumatoid arthritis and other autoimmune diseases, Ignyta’s technology failed in early 2013, Lim said in a recent interview.

Lim (pictured above) was lucky in some respects, though. He had closed on $6 million in financing just a few months earlier. Of the options he faced at the time—forge ahead with the diagnostic tool despite adverse test results, close down the company and return the capital to investors, or come up with an alternative—Lim decided to pivot, and switched Ignyta’s focus from autoimmune diseases to cancer.

Now Lim is awaiting interim results of a global pivotal clinical trial that could determine Ignyta’s ultimate fate. He said he anticipates the company (NASDAQ: RXDX) will disclose its interim findings sometime next spring.

If the results of what Lim calls Startrk-2 confirms the data from a prior clinical trial, in which 24 patients with different solid tumors showed a 79 percent response rate, Ignyta would likely seek FDA approval for entrectinib, its lead drug candidate.

The outcome of the prior clinical trial (Startrk-1) was exciting, Lim said, because patients in the study were diagnosed with seven different tumor types, including non-small cell lung cancer, head and neck cancer, renal cell carcinoma, and melanoma. Despite the variety of tumor types, Ignyta’s genomic analyses showed that all of the patients enrolled in the study had one of five specific gene fusions. Such fusions occur when a piece of one chromosome fuses with part of another chromosome to form an oncogene, an abnormal gene capable of causing cancer.

Fusion oncogenes frequently act alone in driving cancers, Lim said, and the five specific oncogenes are part of a group of cellular signaling pathways that cause aberrant cellular growth. Ignyta’s lead drug candidate targets all five of these oncogenic targets (technically known as TrkA, TrkB, TrkC, ROS1, and ALK), which serve as “on-off” switches on the surface of cells, Lim said.

In its financial presentations, Ignyta also has highlighted that entrectinib crosses the blood-brain barrier, and was highly effective in treating one patient whose non-small cell lung cancer (NSCLC) had spread to the brain. A series of images of the patient, who was treated at Massachusetts General Hospital in Boston, shows a complete response of all brain metastases.

Green lines point to brain tumor that responded to Ignyta drug in an early stage trial. (images courtesy of Ignyta)

Green lines point to brain tumor that responded to Ignyta drug in an early stage trial. (images courtesy of Ignyta)

In the Startrk-2 clinical trial, Lim said scientists at 150 research sites in 15 countries are testing the use of entrectinib on as many as 300 cancer patients who have one of these five oncogenes. The incidence of these oncogenes is rare in more common types of tumors, such as lung and colon cancer, Lim said. But they occur more frequently in rare types of cancer, such as secretory breast cancer and certain head and neck cancers.

These five oncogenes occur in some 30 types of cancer, Lim said, and in many cases, they appear to be the singular driver of the cancer. If that turns out to be the case, targeting these five oncogenes could lead to unusually high response rates for patients with these specific gene fusions.

If Startrk-2 proves to be successful, Lim said Ignyta would likely seek FDA approval for marketing entrectinib in the United States for treating patients who have one of five specific oncogenes—rather than designating the drug for treating certain tumor types, such as non small cell lung cancer or colorectal cancer.

Winning FDA approval for such a “molecular label” would be “unprecedented,” Lim said, explaining that “A molecular label spans all cancer tissues, so long as the appropriate genomic alteration is present.”

Such an approach would require integrating entrectinib with Ignyta’s proprietary diagnostic technologies to ensure that only patients with particular oncogenes would get entrectinib—making Ignyta “the quintessential precision medicine company,” Lim said. The company is taking a similar companion diagnostic approach with other drugs in its development pipeline.

But Ignyta is not the only company that is close to seeking FDA approval for a molecular label. Loxo Oncology (NASDAQ: LOXO), based in Stamford, CT, also has been developing highly targeted anti-cancer drugs matched to patients’ genetically defined cancers. Like Ignyta, Loxo’s lead drug candidate aims to block certain oncogenic targets associated with tropomyosin receptor kinases (TRK).

Looking back at the choices he faced in early 2013, Lim said he made the right decision. “Redefining ourselves as a therapeutic company with a diagnostic edge was good for patients and for us as shareholders,” Lim said.

In the course of three and a half years, Ignyta has grown from just two employees (Lim and chief operating officer Zach Hornby) to roughly 160. The company’s milestones include:

Merging in 2013 with Actagene Oncology, a San Diego startup with a strong drug discovery and development team led by Patrick O’Connor, who had headed a group of successful cancer drug hunters at Pfizer. Ignyta later licensed rights to the anti-cancer compound now known as entrectinib from a former Pfizer lab in Nerviano, Italy.

—Ignyta completed a reverse merger with a defunct public company that traded over the counter in October, 2013, and raised $54 million the following month.

—Ignyta moved to the Nasdaq in 2014, and raised an additional $55 million in its debut there.

“Over the last few years, it’s been nose-down focus on execution for us,” Lim said. But now, if the pivotal trials for entrectinib can demonstrate sufficient safety and efficacy, Ignyta should have a well-defined path to move forward.