Cerulean Pharma
Based: Cambridge, MA
Founded: 2007
Website: www.ceruleanrx.com
CEO: Oliver Fetzer, PhD

The Scoop: Anyone familiar with preclinical drug development will be aware of the promise of nanotechnology. Researchers in the lab for years have been advancing the science of small to repackage therapeutics into tiny delivery vehicles that can more precisely target a disease. Cerulean, however, has taken the basic science and advanced it into a randomized Phase II study now under way for non-small cell lung cancer. So be on the lookout for top-line, proof-of-concept human data in about a year. And on top of their two cancer drug programs, Cerulean scientists are convinced they may have the technology to help re-energize the RNAi field, offering a better approach for delivery and clearing a serious development roadblock that has stymied a slate of companies and spurred some Big Pharma operators to shelve once ambitious programs. That's a lot for a mid-sized biotech. For a small developer with 25 staffers, it's remarkable progress.

What Makes It Fierce: By homing in on tumor cells and releasing packages of a well-known cancer drug right where it's needed, the theory is the little biotech can go after some of the biggest, hardest targets in cancer. By the CEO's reckoning, Cerulean could be nearing breakthrough data on major new therapeutics.

That promise helped lure in Lilly Ventures to take the lead on a $24 million round last fall. Cerulean has raised a total of $57 million from venture backers over the years.

The biotech's nanotechnology--drawn from both Caltech (through a licensing pact with Calando) and MIT--is fascinating. Drug molecules are attached to a polymer that either self-assemble into a standard nanoparticle or are formulated according to a precise design step. Once it enters the cancer cell, the polymer is discarded and flushed naturally, leaving the drug to do its work without causing havoc in healthy cells.

Its lead drug, CRLX101, delivers minute quantities of camptothecin--an experimental cancer drug that had to be abandoned because it was so toxic--through the large pores characteristic of the leaky vasculature found in tumors. Another program coming through the pipeline delivers nano-sized doses of Taxotere, or docetaxel. And its work delivering small interfering RNA offers a whole new program that's been attracting the attention of some of the biggest players in the industry.

In two early cancer studies--a Phase I and IIa that recruited a combined 60 patients--researchers noted signs of efficacy as well as an improved safety profile. Significantly, the patients didn't exhibit some of the classic symptoms of harsh chemotherapies, including hair loss and fatigue.

"We gave patients median, progression-free survival of 3.8 months," says CEO Oliver Fetzer (pictured), who earlier had been head of R&D and corporate development at Cubist. "That's remarkable for advanced non-small cell lung cancer patients." The overall survival rate of these patients taking docetaxel is 8 or 9 months on average, he adds, and adding even a couple of months to that would signify a major advance in the field. 

Now Cerulean will have to proffer hard data showing its lead drug can improve overall survival as a primary endpoint, with progression-free survival being an important secondary endpoint. A clear set of safety data will also be essential before the company can claim success. And the biotech will have to do it in a much larger study, randomizing 150 patients. There's a lot riding on the outcome.

Fetzer for now is thinking it makes the best sense to wait for the "huge inflection point" of top-line data before inking a collaboration deal on the lead program. The second cancer program is in line to begin an eventual Phase I, and the company's growing confidence with nanotech convinced the team it was on to something that could blow up the delivery obstacle slowing down work on RNAi.

Cerulean may require somewhat more venture capital than the biotech has on hand, but the data is on its way. And while a single-program company might be thinking about a sale on promising cancer data, Fetzer for now prefers to concentrate on partnerships as the company considers its next steps. Teaming with a big company interested in RNAi also has potential.

Venture Backers: Lilly Ventures, Bessemer Venture Partners, Polaris Venture Partners, Venrock, Lux Capital and William H. Rastetter.