Cerulean Announces Publication Describing Synergistic Anti-Tumor Activity of CRLX101 with Avastin in Advanced Metastatic Ovarian Tumor Models

Cerulean Pharma Inc. (Nasdaq: CERU), a leader in Dynamic Tumor Targeting™, today announced that Clinical Cancer Research published a manuscript describing preclinical data demonstrating that CRLX101, Cerulean’s proprietary investigational drug, has potent anti-tumor activity alone and in combination with Avastin® (bevacizumab) in advanced metastatic ovarian cancer.

These preclinical data also demonstrate that CRLX101 reduced the up-regulation of HIF-1α by Avastin, which is believed to be a mechanism of resistance to anti-angiogenic therapy. CRLX101 is a dual HIF-1α and topoisomerase-1 targeting nanoparticle-drug conjugate (NDC) currently in clinical studies for multiple cancer types. The manuscript posits that these data support further clinical research of CRLX101 as a single agent, as well as in combination with anti-angiogenic agents like Avastin, where there is an opportunity for highly synergistic activity.

“Patients with ovarian cancer receiving anti-angiogenic therapy experience survival benefits which are diminished by drug resistance, which is believed to be driven at least in part by a treatment-related increase in HIF-1α,” stated Robert S. Kerbel, Ph.D., Sunnybrook Research Institute and a lead author of the paper. “The data presented in this manuscript demonstrate that the combination of CRLX101 and Avastin is synergistic, with the potential to enhance survival of patients with ovarian cancer and reduce drug resistance through the combined mechanisms of durable HIF-1α inhibition and anti-angiogenesis.”

In a model of advanced metastatic ovarian cancer, preclinical data demonstrate that CRLX101 is highly efficacious as a monotherapy. Furthermore, in murine models of advanced ovarian cancer, chronic low-dose CRLX101 with Avastin reduced Avastin-induced HIF-1α up-regulation and resulted in increased efficacy, with minimal toxicity.

“Given these preclinical and initial clinical results published in Clinical Cancer Research, we believe further clinical studies evaluating CRLX101 in combination therapy are warranted in ovarian cancer, and in other cancer types where HIF-1α is implicated in pathogenesis, to potentially improve effectiveness in these patients,” commented Carolyn Krasner, M.D., Massachusetts General Hospital Cancer Center and a lead author of the paper.

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’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.

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.

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