On June 22, 2016 Cerulean Pharma Inc. (NASDAQ:CERU), a clinical-stage company developing nanoparticle-drug conjugates (NDCs), reported the publication of preclinical proof of concept data for its lead compound, CRLX101, in the journal Cancer Research (Press release, Cerulean Pharma, JUN 22, 2016, View Source [SID:1234513504]).

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The publication highlights that CRLX101 demonstrated strong antitumor activity, as monotherapy and in combination with Avastin (bevacizumab), leading to complete tumor regression, reduced metastasis, and extended survival of mice with metastatic disease. These preclinical results were derived from mouse models of orthotropic primary triple-negative breast tumor xenografts, including a patient-derived xenograft and a model of post-surgical, advanced metastatic breast cancer. The article was published online.

"CRLX101 in combination with Avastin is a promising combination that has shown compelling antitumor activity in renal cell carcinoma and ovarian cancer, and we are eager to further explore its potential utility in this aggressive and difficult-to-treat form of breast cancer in which patients are at very high risk of recurrence and metastasis," said Christopher D.T. Guiffre, President and Chief Executive Officer of Cerulean. "Consistent with what we observed in previous studies, these preclinical data show that CRLX101 complements and improves concurrent antiangiogenic therapy, and provides strong rationale for continued development in this indication."

In primary xenograft and patient-derived xenograft models, mice on therapy for five to six months of CRLX101 showed tumor growth suppression or regression and reduced lung metastasis. Additionally, Avastin improved both median survival and reduced lung metastasis. Long-term antitumor activity of CRLX101 monotherapy and combination with Avastin was also demonstrated to prevent the emergence of new metastases and caused regression of existing metastases in a model of post-surgical, advanced metastatic breast cancer. Finally, CRLX101 led to improved tumor perfusion and reduced hypoxia, as measured by contrast-enhanced ultrasound and photoacoustic imaging. This improvement in tumor perfusion may contribute to the ability of CRLX101 to effectively and durably suppress HIF-1α.

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.