Cerulean Announces Publication Showing CRLX101 Localizes Selectively in Human Tumors, Sparing Adjacent Healthy Tissue

Phase 1 Data Published in Proceedings of the National Academy of Sciences (PNAS)

 

WALTHAM, Mass.-- Cerulean Pharma Inc. (CERU), a clinical-stage company developing nanoparticle-drug conjugates (NDCs), today announced the publication of clinical data for its lead compound, CRLX101, in the journal Proceedings of the National Academy of Sciences (PNAS). The publication highlights results from an investigator-sponsored clinical trial, in which pre- and post- treatment tumor biopsies from patients with gastric cancer treated with CRLX101 show the presence of CRLX101 and its payload, camptothecin, in tumors, and their absence in surrounding normal tissue. Importantly, inhibition of the molecular targets of CRLX101 was demonstrated in post-treatment biopsies. The article was published online. Initial results from the trial were presented at the 2015 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics on November 7, 2015.

“CRLX101 delivers a powerful anti-cancer drug to the tumor, sparing adjacent healthy tissue, results that directly translate observations from the lab to the clinic,” stated Mark Davis, Ph.D., Warren and Katharine Schlinger Professor of Chemical Engineering at California Institute of Technology. “Toxicities prevented the clinical development of camptothecin. Creating an NDC that incorporates camptothecin as its payload overcomes this major hurdle.”

 

“The data Dr. Davis and colleagues at the City of Hope Comprehensive Cancer Center published in PNAS demonstrate the power of NDCs,” said Christopher D.T. Guiffre, President and Chief Executive Officer of Cerulean. “Dynamic tumor targeting is no longer something we have shown only in rodents – it has now been confirmed in humans with CRLX101. Targeting tumors and sparing healthy tissue has long been a major objective of oncology drug development, and CRLX101 achieves that important goal.”

 

The article describes results from nine patients with advanced gastric cancer enrolled in a pilot study sponsored by the City of Hope Comprehensive Cancer Center. All patients progressed on at least one prior line of systemic therapy. Tumor and adjacent healthy tissue biopsies were obtained through endoscopic-assisted biopsies prior to and 24 - 48 hours after receiving 15 mg/m2 of CRLX101. In all nine patients, the CRLX101 payload, camptothecin, was detected in patient tumor tissue and neither CRLX101 nor camptothecin was detected in post-treatment healthy tissue samples adjacent to tumors. Immunohistochemistry in patient tumors demonstrated that sufficient camptothecin is released from CRLX101 in the post-treatment tumors to have the intended biological effects of inhibiting its molecular targets, topoisomerase-1 and hypoxia inducible factor 1α, two proteins that are believed to be involved in the progression of the cancer.

 

About Mark Davis

 

Mark Davis, Ph.D., is the Warren and Katharine Schlinger Professor of Chemical Engineering at the California Institute of Technology and a member of the City of Hope Comprehensive Cancer Center. Dr. Davis is a pioneer in the field of nanotechnology. He was elected to the National Academy of Engineering, the Institute of Medicine, and the National Academy of Sciences. He has won a number of awards, including the Presidential Young Investigator Award from the National Science Foundation, the Donald Breck Award from the International Zeolite Association, the Alan T. Waterman Award from the National Science Foundation, and in 2014 the Prince of Asturias Award for Technical and Scientific Research from the King of Spain, among others. He sits on the editorial board of Molecular Therapy-Nucleic Acids, Drug Delivery and Translational Research, Proceedings of the National Academy of Science, and Nucleic Acid Therapeutics, among other publications.

 

About CRLX101

 

CRLX101 is a nanoparticle-drug conjugate (NDC) designed to concentrate in tumors and slowly release its anti-cancer payload, camptothecin, inside tumor cells. CRLX101 inhibits topoisomerase 1 (topo 1), which is involved in cellular replication, and also inhibits hypoxia-inducible factor-1α (HIF-1α), which research suggests is a master regulator of cancer cell survival mechanisms. CRLX101 has shown activity in four different tumor types, both as monotherapy and in combination with other cancer treatments. CRLX101 is in Phase 2 clinical development and has been dosed in more than 350 patients. The U.S. FDA has granted CRLX101 Orphan Drug designation for the treatment of ovarian cancer and Fast Track designation in combination with Avastin® in metastatic renal cell carcinoma.

 

About CRLX301

 

CRLX301 is a dynamically tumor-targeted NDC designed to concentrate in tumors and slowly release its anti-cancer payload, docetaxel, inside tumor cells. In preclinical studies, CRLX301 delivers up to 10 times more docetaxel into tumors, compared to an equivalent milligram dose of commercially available docetaxel and was similar to or better than docetaxel in seven of seven animal models, with a statistically significant survival benefit seen in five of those seven models. In addition, preclinical data show that CRLX301 had lower toxicity than has been reported with docetaxel in similar preclinical studies. CRLX301 is in Phase 1/2a clinical development.

 

About Cerulean Pharma

 

The Cerulean team is committed to improving treatment for people living with cancer. We apply our Dynamic Tumor Targeting™ Platform to create a portfolio of NDCs designed to selectively attack tumor cells, reduce toxicity by sparing the body’s normal cells, and enable therapeutic combinations. Our first platform-generated NDC clinical candidate, CRLX101, is in multiple clinical trials in combination with other cancer treatments, all of which aim to unlock the power of combination therapy. Our second platform-generated NDC clinical candidate, CRLX301, is in a Phase 1/2a clinical trial. For more information, please visit www.ceruleanrx.com.

 

About Cerulean’s Dynamic Tumor Targeting™ Platform

 

Cerulean’s Dynamic Tumor Targeting Platform creates NDCs that are designed to provide safer and more effective cancer treatments. We believe our NDCs concentrate their anti-cancer payloads inside tumors while sparing normal tissue because they are small enough to pass through the “leaky” vasculature present in tumors but are too large to pass through the wall of healthy blood vessels. Once inside tumors, our NDCs enter tumor cells where they slowly release anti-cancer payloads from within the tumor cells.

 

Cautionary Note on Forward Looking Statements

 

Any statements in this press release about our future expectations, plans and prospects, including statements about the clinical development of our product candidates, statements about our estimated research and development expenses and sufficiency of cash to fund specified use of cash and other statements containing the words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “hypothesize,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “would,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: the uncertainties inherent in the initiation of clinical trials, availability and timing of data from ongoing and future clinical trials and the results of such trials, whether preliminary results from a clinical trial will be predictive of the final results of that trial or whether results of early clinical trials will be indicative of the results of later clinical trials, expectations for regulatory approvals, availability of funding sufficient for our foreseeable and unforeseeable operating expenses and capital expenditure requirements and other factors discussed in the “Risk Factors” section of our Annual Report on Form 10-K filed with the Securities and Exchange Commission on March 10, 2016, and in other filings that we make with the Securities and Exchange Commission. In addition, any forward-looking statements included in this press release represent our views only as of the date of this release and should not be relied upon as representing our views as of any subsequent date. We specifically disclaim any obligation to update any forward-looking statements included in this press release.

 

Avastin is a registered trademark of Genentech, Inc.

 

 

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