Off the coast of the Bahamas, in sea grass more than a half-mile deep, San Diego-based Nereus Pharmaceuticals found a fungus that may be the key ingredient for an innovative new cancer drug. This will be a key year for gathering evidence that will either support or debunk the idea.
I got the download on Nereus last week in a conversation with co-founder and CEO Kobi Sethna and Charles White, the company’s chief business officer. Nereus has raised a whopping $125 million in venture capital in almost a decade of business, from big name investors like Roche Venture Fund, Alta Partners, and San Diego-based Forward Ventures, among others, so I figured it was worth taking a look.
The company is built on the idea that many of the biggest pharmaceutical breakthroughs, like penicillin, come from natural microbes. The bulk of these fungi and bacteria that led to drugs come from land, but, of course, Mother Nature has plenty of more biodiversity in the ocean. After years of sailing expeditions that trawled up potential drug candidates in hot and cold water, shallow and deep, from the Pacific and the Atlantic, Nereus has looked at hundreds of candidates for treating autoimmune disease and cancer—and now has settled on two lead horses against cancer that it thinks have a real shot. So the sailing expeditions are over, and now it’s time to push through the hard, unpredictable slog of clinical trials to see if these drugs really work in people.
“In this business, you’ve got to be focused. It’s the name of the game,” Sethna says. “We’ve morphed into an oncology company.”
So what does Nereus have to show for all that investment? The lead candidate (the one found off the coast of the Bahamas) is called NPI-2358. It’s a small-molecule drug synthesized in the lab to be similar in structure to a unique fungus it found in the ocean. This drug is designed to be a “vascular disrupting agent” to tumors. It’s made to attack existing blood vessels in tumors, unlike big-name cancer drugs like Genentech’s bevacizumab (Avastin) or Pfizer’s sunitinib (Sutent) that are meant to block the formation of new blood vessels to tumors, White says.
The reason the Nereus drug is still alive in the clinic is that it showed a long-lasting, potent ability to disrupt tumor blood flow, without causing the heart damage that has plagued other vascular-disrupting drugs in the class, White says. The first clinical trials supported further testing, confirming the drug wasn’t harming the heart while shrinking tumors at least partially for about three-fourths of patients when given in combination with Sanofi-Aventis’ docetaxel (Taxotere).
This molecule is in competition with Waltham, MA-based Oxigene’s OXi4503, which is in early clinical trials, and about “five or six others” still in animal testing, White says. The advantage he sees with the Nereus drug is that it appears to enhance the effectiveness of chemotherapy, without adding on any new layers of toxic side effects, as often happens with chemo cocktails. The drug is currently being tested against lung cancer, the leading cancer killer in the U.S.
The second drug, called NPI-0052, requires a little more science explanation. It’s a proteasome inhibitor, derived again from an ocean bacteria called an actinomycete. It’s meant to be a second-generation drug following behind the success of Takeda Pharmaceutical’s bortezomib (Velcade). Drugs in this class are meant to disable the action of enzymes that normally clean up debris in cells. When this ability is disrupted, proteins build up in the tumor cells, sending them into a self-destruct mode called apoptosis. The Nereus drug is thought to block more of the proteasome sites on cells, providing a more effective shutdown, White says. Early trials also suggest the Nereus drug doesn’t cause nerve damage in the hands and feet that limits usage of the Takeda rival, and may work in patients who resist the other treatment. “We don’t get the side effect issue that limits Velcade. Our safety profile is far better,” White says.
That’s a bold thing to say about a competitor that exceeded $1 billion in sales last year, especially when his company’s contender is still in the first of three phases of clinical trials. Nereus, with 25 to 30 employees, has no drugs on the market. By the end of this year, the company expects to have data on its first drug— NPI-2358. —from a trial of 154 patients with non-small-cell lung cancer. Like many companies, Nereus hopes to capture the attention of the leading lights in cancer research at the top two industry conferences of the year, the American Society of Clinical Oncology in late May/early June and the American Society of Hematology in December.
Whatever data is revealed at those meetings will go a long way toward determining if Nereus really can sink or swim (sorry for the ocean pun, but couldn’t resist.) Even in the recession, we’ve seen signs lately in Boston (Vertex Pharmaceuticals) and in Seattle (Seattle Genetics) that companies that can deliver stellar clinical trial results can still be rewarded with financing or partnerships to take them through the most expensive, final phase of development to win FDA approval. Nereus can only hope its data turns out according to plan, and that investors or partners will still be in the mood to finance of its progression to the ultimate proving ground in development—Phase III clinical trials.
“We can’t do anything until we prove these products deliver the kind of data that we’re looking for,” Sethna says.