Cerulean Pharma Inc., a leader in dynamically tumor-targeted nanopharmaceuticals, today announced the publication of translational data on the company's lead candidate, CRLX101, currently in Phase 2 trials. The study results, which are published in PNAS, indicate that animal pharmacokinetic and pharmacodynamic data are translatable to humans.
Results from Phase 1 and 2 clinical trials that have been correlated to preclinical data and discussed in the paper include:
A consistent manufacturing process across numerous lots of CRLX101 was observed, as evaluated by particle size, polymer molecular weight and drug loading, resulting in no significant differences in pharmacokinetics or urinary excretion in patients treated with more than one clinical lot.
Low patient-to-patient variations in plasma concentrations of CRLX101, unlike what has been observed with liposomes.
Similar time- and concentration-dependent behavior of camptothecin concentration between patients and animals.
Consistent pharmacokinetics upon repeat dosing in patients.
Predictable release kinetics of camptothecin that is largely enzyme independent.
Slow release over time of the drug once in tumors, leading to a durable inhibition of topoisomerase 1.
Deep permeation of intact nanoparticles in mouse and human tumors, which will enable the killing of tumor cells far from the vasculature.
"CRLX101 is designed to preferentially target tumors through leaky neovasculature, achieve uptake into cancer cells, and release its payload over time from within the cancer cells," said Mark E. Davis, professor of chemical engineering at the California Institute of Technology, scientific advisor to Cerulean, and inventor of CRLX101.
Scott Eliasof, vice president of research at Cerulean, commented: "It's difficult to obtain data on how nanoparticles work in humans. As a result, this evaluation comparing clinical trial and preclinical studies is valuable because it demonstrates that in the case of CRLX101, animal studies are a strong predictor of results in human trials."
The paper, "Correlating preclinical animal studies and human clinical trials of a multifunctional, polymeric nanoparticle," was co-authored by Mark E. Davis of the California Institute of Technology, Scott Eliasof of Cerulean Pharma, and others at Cerulean, Calando Pharmaceuticals, City of Hope Comprehensive Cancer Center and the California Institute of Technology. It is available at http://www.pnas.org/content/early/2013/08/21/1309566110.full.pdf+html.
CRLX101 is an investigational anti-cancer agent that inhibits topoisomerase 1 (Topo 1) and hypoxia-inducible factor-1a (HIF-1a). Topo 1 is an essential cell replication enzyme and a commercially validated anti-cancer target. HIF-1a is a master regulator of cancer cell survival mechanisms such as cancer stem cell formation and is upregulated under hypoxic conditions created by traditional cancer therapies, for example anti-angiogenic agents and radiation. To date, HIF-1a has been undrugable. CRLX101 is a dynamically tumor-targeted nanopharmaceutical designed to concentrate in tumors and release its payload, camptothecin, over an extended period of time, prolonging drug exposure at the site of action. CRLX101 has been dosed in more than 200 patients, many for more than six months. Anti-tumor activity (multiple RECIST responses and prolonged stable disease) has been observed in three different tumor types in highly refractory treatment settings, as monotherapy and in combination with Avastin®. CRLX101 is currently in Phase 2 clinical development. More information on CRLX101 clinical studies can be found at clinicaltrials.gov.
About Cerulean Pharma Inc.
Cerulean Pharma Inc. is a clinical-stage company specializing in the development of dynamically tumor-targeted nanopharmaceuticals. Cerulean is applying its proprietary nanopharmaceutical platform to advance a new class of therapeutic agents to address significant unmet medical needs. With an initial focus in oncology, the Company's technology platform can be applied to a wide range of drug molecules, ranging from small molecules to peptides and RNAs. Cerulean is privately held and funded by leading investors, including Polaris Venture Partners, Venrock, Lilly Ventures, Lux Capital, and CVF, LLC. Cerulean is located in Cambridge, Massachusetts. For more information, please visit the Company's website at ceruleanrx.com.