Cerulean Pharma Makes Progress in Attacking the Big C with Tiny Drugs

Xconomy Boston — 

Cerulean Pharma has made lots of progress since its early days in 2007 when I first visited the biotech startup, then called Tempo Pharmaceuticals, and company chairman Alan Crane broke out his laptop to show me an animation of the newly hatched firm’s nanoparticle drugs congregating inside tumors and killing them.

The Cambridge, MA-based startup, which has raised $37 million, is now working on building clinical-trial evidence that its lead nanoparticle drug can kill tumor cells for real. Oliver Fetzer, Cerulean’s chief executive, also told me that the firm is working on raising a new funding round to bring the drug, dubbed CRLX101, further into clinical development for treating solid tumors while developing earlier-stage molecules as well.

There’s been lots of hype about the promise of nanotechnology in medicine. Cerulean is a rare case of a firm that has shown its nanoparticles could be safe for humans while delivering some of the hoped-for benefits of the tiny molecules. The company reported late last month that its lead drug was well tolerated in an initial human study. With that data, it has begun enrolling patients into its next, Phase IIa, clinical trial, which aims to provide more evidence of the drug’s ability to treat solid tumors such as lung cancer, Fetzer said. Cerulean is further along in clinical development that its local rival in the nanoparticle-based cancer drug field, Cambridge-based Bind Biosciences.

Already, Cerulean has seen how its lead nanoparticle, which contains the anti-cancer compound camptothecin, helps keep the active drug inside tumors for much longer than if the patient received the compound alone. The nanoparticle also large enough to keep it from being removed from the body by the kidneys, where it could cause side effects, but small enough to enter tumor cells to deliver the cancer-killing agent. Development of camptothecin as a stand-alone cancer drug had been scrapped years ago because of the compound’s toxic side effects, but Cerulean’s nanoparticles might be able to limit those effects by keeping the drug concentrated in the tumor cells and away from healthy tissues.

“Cerulean is at this point the only the company that has an advancing clinical program that is a true single drug nanopharmaceutical,” Fetzer said.

His point is debatable, he acknowledged. Abraxis BioScience, which Summit, NJ-based Celgene (NASDAQ:CELG) agreed to buy for $2.9 billion in June, has gained FDA approval for an earlier nanoparticle drug that delivers a chemotherapy agent for treating lung and breast cancers. However, Fetzer said, that nanoparticle does not stay intact for long once it enters the body, whereas Cerulean’s nanoparticles are designed to hold together all the way until they reach the interior of tumor cells. The particles are intended to provide greater control over when its active drug compound is released than earlier nanoparticles.

Such control could also make Cerulean’s nanoparticles useful in overcoming challenges in delivering other types of drugs, including the gene-silencing treatments called short interfering RNAs, Fetzer said. These molecules, under development at firms such as Cambridge, MA-based Alnylam Pharmaceuticals (NASDAQ:ALNY), are made of nucleic acid chains, which can easily be degraded by enzymes in the body before they can reach diseased cells, and Cerulean’s nanoparticles might be able to help shield them on that journey. Fetzer told me that his firm is actively working on research in RNA drug delivery, but he declined to provide specifics.

When I first met with Crane, then chief executive, at Cerulean three years ago, his story about the startup was very much a science one. (Crane, a general partner at Polaris Venture Partners in Waltham, MA, turned over the reigns to Fetzer last year.) The company’s scientific founders are MIT biological engineering professor Ram Sasisekharan, who also founded Cambridge’s Momenta Pharmaceuticals (NASDAQ:MNTA), and Shiladitya Sengupta, an assistant professor at Harvard Medical School. Last year, the company also licensed technology from the lab of renowned Caltech chemical engineer Mark Davis that is related to Cerulean’s lead drug. The firm’s original nanoparticle technology from MIT is used in the firm’s pre-clinical candidate that will deliver the chemotherapy drug docetaxel.

Fetzer said he is working on raising a new round of venture capital from the startup’s existing backers—which include Polaris, Lux Capital, Bessemer Venture Partners, and Venrock Associates—and at least one new venture investor. The CEO declined to say when he planned to close the new round, which would be the company’s third. (Bob Tepper, a partner at Boston-based Third Rock Ventures, is an independent member of the board at Cerulean but his firm is not an investor, according to the company.) The plan is to use the new capita to fund the completion of the Phase IIa trial, which is expected to yield results sometime in mid-2011.

For non-small cell lung cancer, to name one tumor type of interest in the Phase IIa, the median survival of patients who have failed to respond to existing drugs is about seven months, Fetzer said. Soon, Cerulean will learn whether, and how much, its drug can improve on that dismal figure. “We will be able to show over the course of the rest of this year what a difference our drug can make,” Fetzer said.