Despite a phase IIb miss this time last year for lead compound CRLX101 in advanced non-small-cell lung cancer (NSCLC), Cerulean Pharma Inc. vowed to plow forward with its nanopharmaceutical platform. After dosing the first patient last month in a phase II trial of CRLX101 in combination with Avastin (bevacizumab, Roche AG) in relapsed ovarian cancer, the company is moving ahead in a big way, filing Monday with the SEC to raise up to $75 million in an initial public offering.

The Cambridge, Mass.-based company was founded in late 2006 as Tempo Pharmaceuticals, based on technology exclusively licensed from the Massachusetts Institute of Technology. In 2008, the company changed its name to Cerulean, derived from the Latin word for “heaven or sky,” to reflect the potential of its platform to advance cancer therapy.

The same year, Cerulean added $10 million in a series B-1 financing, padding its $8 million series B in 2008 on top of a $12.1 million series A in 2007. (See BioWorld Today, July 28, 2009.)

In all, the company pulled in $69.1 million in disclosed venture funding across five rounds. Following its co-founding and seed financing by Polaris Venture Partners, Cerulean added Venrock, Lux Capital, CVF LLC and Lilly Ventures as major investors. (See BioWorld Today, Nov. 16, 2010.)

The steady cash flow helped Cerulean to advance its lead program, then dubbed IT-101, which it picked up in 2009 from Pasadena, Calif.-based Calando Pharmaceuticals Inc. for undisclosed up-front, milestone and royalty payments. Camptothecin was discovered as a potential cancer drug decades ago but proved too toxic in its original form for use in treatment. Cerulean’s nanopharmaceutical is a dual inhibitor of topoisomerase-1 and hypoxia-inducible factor-1α designed to deliver camptothecin directly to tumors, sidestepping troublesome systemic side effects.

However, Cerulean ran into a setback last year when CRLX101 missed its endpoint of overall survival (OS) in advanced NSCLC. The 157-patient trial in Russia and the Ukraine tested CRLX101 added to best supportive care, compared to best supportive care alone. Patients in the study had progressive disease following one or two different chemotherapy regimens. The study also examined safety and tolerability, and patients were monitored for progression-free survival (PFS), objective tumor response and pharmacokinetic parameters. (See BioWorld Today, March 25, 2013.)

CRLX101 continued in a phase II study in relapsed small-cell lung cancer (SCLC) in comparison with topotecan (Hycamtin, Glaxosmithkline plc), an analogue of camptothecin. At the time, Oliver Fetzer, president and CEO of the Cambridge, Mass.-based firm, told BioWorld Today that “there’s a very strong biological link that we’re pursuing. We know [our] drug is very well tolerated, which you can’t say of topotecan.”

To date, the University of Chicago-sponsored SCLC trial remains open and is recruiting 156 patients into two cohorts, with PFS as the primary endpoint, according to Thomson Reuters Cortellis Clinical Trials Intelligence (CTI). Secondary endpoints include separate assessments of OS and response rates using RESIST criteria in each cohort as well as continuous change in tumor size across the study population.

At this point, however, Cerulean is mainly focused on advancing CRLX101 in three other indications: relapsed renal cell carcinoma (RRCC), relapsed ovarian cancer and neoadjuvant rectal cancer. A phase Ib/II open-label investigator sponsored trial (IST) of CRLX101 in combination with Avastin is under way in patients with RRCC. The company expects to begin a randomized phase II, also in combination with Avastin, in the second half of the year.

The first, a single-arm trial of CRLX101 as monotherapy in relapsed ovarian cancer, completed enrollment and met its primary endpoint, with at least four patients achieving PFS time on trial of six months or longer. Platinum-resistant ovarian cancer patients are being enrolled in the second, single-arm combination trial of CRLX101 and Avastin. Assuming positive findings from the second part of the trial, Cerulean plans to initiate a pivotal study of the compound, in combination with Avastin, in the indication next year.

A phase Ib/II open-label IST of CRLX101 in combination with chemoradiotherapy, consisting of Xeloda (capecitabine, Teva Pharmaceutical Industries Ltd.) and radiotherapy, is under way in patients with rectal cancer receiving treatment prior to surgery. Findings from that study could lead to the launch of a randomized phase II this year.

CRLX301, the second candidate from the company’s dynamic tumor targeting platform, is a nanopharmaceutical with docetaxel as its anticancer payload. According to its S-1, Cerulean plans to move CRLX301 into its first human study by year-end.

The company holds full global rights to both compounds.

In its filing, Cerulean reported 11.4 million shares of common stock outstanding as of Jan. 31. The company had $5.5 million in cash and equivalents and an accumulated deficit of $94.33 million as of Dec. 31, 2013, according to the filing. In August 2013, Cerulean issued and sold an aggregate of $8.8 million in 7 percent convertible promissory notes to its officers, directors and major shareholders as a bridge financing, and in February 2014, the company issued and sold $6 million in 7 percent convertible promissory notes.

Cerulean, which filed as an emerging growth company under the Jumpstart Our Business Startups Act of 2012, plans to list on the Nasdaq Global Market as CERU.

The company did not disclose the number of shares or pricing of the offering but said it plans to grant the underwriters a 30-day option to purchase additional shares to cover overallotments. Leerink Partners LLC is sole bookrunner on the deal.