Endocyte faces big decisions with new cancer drug

Endocyte Inc. reported Saturday night that its drug vintafolide extended the lives of certain lung cancer patients about six months longer than an existing therapy.

That’s great news for West Lafayette-based Endocyte because that same drug, just five months ago, suffered a shocking failure as an ovarian cancer treatment.

“These data reinforce our confidence in the potential of Endocyte's technology platform,” Daniel Brims, an analyst at Cantor Fitzgerald, said in a research note Monday morning.

Endocyte’s stock promptly jumped 10 percent Monday morning, but then gave up those gains and entered negative territory.

Uncertainty persists because Endocyte’s path forward is far from clear.

Vintafolide’s success in one form of lung cancer—known as adenocarcinoma—is enough to produce a blockbluster drug because adenocarcinoma accounts for 40 percent of all lung cancer cases in the United States.

But Endocyte has another drug, EC1456, said by company officials to be roughly 20 times more powerful as a chemotherapy agent than vintafolide, and it is in early phases of human testing.

CEO Ron Ellis said Endocyte has the financial resources to advance both drugs into phase 3 clinical trials—the last and most expensive stage of human testing before submitting a drug to regulators for market approval. Endocyte officials estimate a Phase 3 trial of vintafolide would enroll 600 patients and cost $50 million.

“Our financial strength enables us to explore moving forward with more than one of our wholly owned pipeline agents in select indications should it be the most beneficial path for the company and patients,” Ellis said in a prepared statement.

But some analysts think Endocyte has only enough cash—about $219 million—to bring one, not both, of the drugs to market.

“We believe Endocyte currently has the resources to only advance a single asset into Phase 3 development,” wrote Brims, the Cantor Fitzgerald analyst. “We expect Endocyte to advance EC1456 into phase 3 over vintafolide if an efficacy signal is observed with greater safety and tolerability at equivalent dose levels.”

All analysts expect Endocyte officials to make a decision on its drug pipeline sometime next year.

Endocyte’s approach to fighting cancer is to take well-known chemotherapy molecules and attach them to a naturally occurring vitamin called folate. Many patients have cancer cells that have far more places on their surfaces for folate to attach than is the case for non-cancerous cells in the body.

As a result, Endocyte’s drugs are designed to attack cancer cells without attacking non-cancerous cells. That feature allows Endocyte to give patients a much higher dose of chemotherapy drugs, without inducing serious side effects, than if those chemotherapy drugs were given by themselves.

The difference between vintafolide and EC1456 is that Endocyte’s scientists have figured out how to attach a chemotherapy agent that is 20 times more powerful than the one used in vintafolide, while keeping the side effects even lower.

The reason side effects should be less is that excess amounts of vintafolide are cleared out of the body via the liver and the digestive tract; that process causes the side effects. Those side effects forced Endocyte to keep the dose of vintafolide somewhat smaller, limiting its effectiveness against the cancer cells.

But EC1456 has been altered to dissolve better in water, so it is cleared out of the body via the kidneys; scientists hope that path will cause fewer side effects. That should allow Endocyte to give patients a chemotherapy dose 70 percent larger in EC1456 than in vintafolide.

So naturally, Endocyte executives think EC1456 will show greater effect on lung cancers, as well as ovarian cancer, endometrial cancer, and three other conditions for which Endocyte is testing it.

“Vintafolide really reflects what we knew in about 2001. Now, 1456 reflects what we know in 2013. A decade of research and work. And that’s why we’re pretty optimistic about the new drugs,” Ellis said in an interview last month. “I know they’re better. They’re significantly better. Now how they’ll do in clinic—you know, I’ve learned my lesson—you have to run the drill and find out. But we have a lot of optimism about those new drugs.”