Syndax Pharmaceuticals has spent eight years trying to show it can make existing cancer drugs work better by switching off certain enzymes implicated in tumor mutation. Now, it has landed enough cash to see if its first drug testing that concept can clear its biggest hurdle yet—a late-stage clinical trial.
Waltham, MA-based Syndax is announcing today that it has secured $26.6 million in equity financing to push its lead drug candidate, a cancer treatment known as entinostat, into a Phase 3 clinical trial. If the trial succeeds, it should provide the last piece of evidence Syndax needs to file an application for FDA approval. Existing investors Domain Associates, MPM Capital, Forward Ventures, and RusnanoMedInvest provided the Series B round. Syndax, co-founded by Domain and scientists from San Diego’s Salk Institute for Biological Studies in 2005, has now raised more than $80 million since its inception, according to CEO Arlene Morris.
The National Cancer Institute is also funding a “significant piece” of the trial, which enables Syndax to combine it with the new equity financing to run this big, ambitious study without the help of a large pharmaceutical partner, Morris says.
Syndax originally got its drug candidate through a license from Bayer. The drug is supposed to treat cancer by building on scientists’ growing understanding of epigenetics—the study of activating or deactivating genes without changing the underlying DNA. This isn’t new: several companies such as Celgene and Merck have used epigenetics to create cancer drugs, while others such as Epizyme are in the midst of doing so. But while Epizyme, for one, is using that approach to home in on certain rare cancers, Syndax is taking a different approach. Syndax hopes its compound will stand out based partly on its ability to selectively hit histone deacetylases, or HDACs, that are most relevant to tumors.
Rather than position its drug in the market as a direct anti-tumor agent, Syndax envisions it being most useful in combination therapy. Researchers believe, for instance, that breast tumor cells undergo epigenetic changes that make them resistant to hormone therapies like aromatase inhibitors. These therapies, which block the production of estrogen, are used to treat postmenopausal women with certain forms of breast cancer that are driven by estrogen production. Syndax is attempting to use its epigenetic drug candidate to make the tumor cells vulnerable to aromatase inhibitors again.
Morris says that this would enable women with breast cancer that has spread to continue with more cycles of hormone therapy before shifting to chemotherapy, which has much stronger side effects.
“The goal is to keep women from going onto chemotherapy as long as possible,” she says.
Syndax completed a mid-stage clinical trial in 2011 that tested its drug in combination with a hormone therapy, exemestane (marketed by Pfizer as Aromasin), in 130 postmenopausal women with what’s known as estrogen-receptor, or ER-positive metastatic breast cancer, after they had stopped responding to hormone therapy on its own. Syndax says its drug showed enough promise in that trial to advance to a larger, Phase 3 study with a similar design. The plan is to randomly assign patients to either a hormone therapy and the Syndax drug, or hormone therapy and a placebo. The co-primary goals of that study will likely be both showing that the treatment combination makes patients live longer, and that it keeps their tumors from spreading, according to Morris.
Syndax has been trying to make similar headway in non-small cell lung cancer, but hasn’t had the same success so far. The company failed a mid-stage clinical trial in which it added its drug candidate to a regimen including mainstay therapies like erlotinib (Tarceva, sold by Genentech and Astellas Pharma). And though Syndax did notice that a subgroup of patients with high levels of a protein called e-cadherin appeared to have better results than those that didn’t, it still has work to do to find the right niche in lung cancer. Morris indicated, for instance, that Syndax will likely go back and do a more targeted mid-stage study, designed to select the patients most likely to benefit.
Syndax is now in the deep end of the pool, where the dollars get larger, the studies get bigger, and the drug is going to have to show a real tangible benefit for patients to make it—especially in a crowded treatment field like breast cancer. Morris says the product is being positioned to offer an advantage to patients they can’t get from any other drug, and the clinical trial results will determine how it ultimately appeals to doctors and patients.
Syndax doesn’t need a partner to fund the coming study, but it hopes to put a partnership together to help develop the drug in other disease types and sell it overseas, Morris says.
Morris, the former CEO of Palo Alto, CA-based Affymax, was asked to step in as CEO in April 2012 because the company was shifting to the later stages of development, and she had experience running a company at that critical juncture. She also gained experience there interacting with Wall Street, and she hinted that Syndax may consider an IPO when the time comes for its next round of funding.
“[We’re] probably at the upper end of what you’d want to raise privately,” she says. “[An IPO] would be on the list [of financing options].”