Cancer cells are sneaky and, unfortunately, smart enough to develop a host of ways to escape the body’s defense mechanisms.
A startup called Oncotide Pharmaceuticals is hoping to outsmart some cancer cells by modulating a certain kind of protein phosphatase that impedes the ability of cancer cells to grow and replicate.
That phosphatase is PP2A, and researchers have acknowledged it as a tumor suppressor because of the role it plays in deactivating oncogenetic kinases that control the proliferation of cells in several kinds of cancers.
But cancer cells have developed ways to stop PP2A so that they can continue to grow. One of those ways is by producing in excess a protein known as SET, which Oncotide says it does in as many as half of primary tumors in a variety of cancers including leukemia, breast cancer and lung cancer. In cells where SET is over-expressed, PP2A is unable to deactivate those oncogenetic kinases, so cancer cells can continue forming and surviving.
Oncotide’s lead candidate, OP449, is designed to deactivate the SET protein and restore the tumor-suppressing functions of PP2A. It says the compound is not toxic to normal cells because PP2A activity is not suppressed in normal cells. In preclinical studies, Oncotide says its compounds have demonstrated the ability to inhibit growth of primary human breast and pancreatic cancer cells and to kill primary human leukemia cells. CEO Mike Vitek said it’s also demonstrated synergistic activity with compounds designed to inhibit the oncogenetic kinases like Genentech/Roche’s Herceptin.
Initially, Oncotide will focus its development on killing cancer cells in hematological cancers like leukemia. This has been one of the fastest-growing markets in cancer drugs in recent years. Gilead has done a series of deals to acquire potential therapeutics for blood cancers, and Ariad Pharmaceuticals and Pfizer saw U.S. Food and Drug Administration approvals in this space last year. Numerous other Big Pharmas have leukemia drugs in their pipelines as well.
Oncotide, which has to this point been funded with SBIR, STTR and DOD grants, is pursuing a $15 million series A to fund IND-enabling studies, which Vitek expects will take nine to 12 months, and a phase IB/IIA proof-of-concept study in humans.
Vitek, an associate professor of neurology at Duke University Medical Center, founded Oncotide in February 2011 with technology licensed from his previous company, Cognosci Inc. It’s based in Research Triangle Park, North Carolina.
[Diagram from Oncotide Pharmaceuticals]