Cerulean Announces Publication Showing CRLX101 Targets Breast Cancer Stem Cells and Impedes Resistance to Anti-angiogenic Therapy in Preclinical Models

Cerulean Pharma Inc. (Nasdaq:CERU), a leader in Dynamic Tumor Targeting™, today announced the publication of a manuscript in Breast Cancer Research and Treatment, describing preclinical data that demonstrate CRLX101, Cerulean’s lead proprietary investigational drug, targets breast cancer stem cells and impedes resistance to anti-angiogenic therapy in breast cancer mouse models.

The results of the study demonstrate that CRLX101, a dual topoisomerase-1 and HIF-1α inhibitor, blocks the HIF-1α mediated increase in cancer stem cells induced by Avastin® (bevacizumab) in a triple-negative breast cancer xenograft mouse model. The up-regulation of HIF-1α by Avastin is believed to be a mechanism of resistance to anti-angiogenic therapy. The combined effects of CRLX101 plus Avastin on cancer stem cells and bulk tumor cells resulted in significant tumor shrinkage and delayed recurrence in this model. The manuscript posits that these data provide a compelling rationale for combining CRLX101 with angiogenic agents in patients with cancer where HIF-1α mediated increases in cancer stem cells may play a role in chemoresistance. The article, “CRLX101, an investigational camptothecin-containing nanoparticle-drug conjugate, targets cancer stem cells and impedes resistance to anti-angiogenic therapy in mouse models of breast cancer” by Conley, et al, was published in the April 2015 issue of Breast Cancer Research and Treatment.

“The preclinical data presented in this manuscript suggest that further study is warranted to assess whether the efficacy of anti-angiogenic drugs can be improved through combination with CRLX101, by reducing drug resistance with the combined mechanisms of durable HIF-1α inhibition and anti-angiogenesis,” stated Max S. Wicha, M.D., Professor, Department of Internal Medicine, Director, University of Michigan Comprehensive Cancer Center and author of the paper. “There is emerging evidence that the induction of hypoxia and up-regulation of HIF-1α is one mechanism contributing to the development of resistance to angiogenic therapies. HIF-1α is believed to be a master regulator of the cellular response to hypoxia, and regulates many cancer cell survival pathways. These key pathways include angiogenesis and cancer stem cells, which are the small number of cells within a tumor with the capacity to metastasize and regenerate tumors.”

About CRLX101

CRLX101 is a dynamically tumor-targeted 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 hypoxia-inducible factor-1α (HIF-1α), which research suggests is a master regulator of cancer cell survival mechanisms thought to promote drug and radiation resistance. CRLX101 has shown activity in four different tumor types, both as monotherapy and in combination with other cancer treatments. CRLX101 is currently in Phase 2 clinical development and has been dosed in more than 250 patients.

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 superior to 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 currently in Phase 1 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 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 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.

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