Cerulean, AstraZeneca and NCI to assess efficacy of CRLX101 and Lynparza combination

The Phase I/IIa trial, which is anticipated to start in the first half of 2016, will be funded and carried out by the NCI on about 55 patients. The companies will supply the products.

Cerulean’s CRLX101 is a nanoparticle-drug conjugate designed to concentrate in tumors and release its anti-cancer payload, camptothecin, inside cancer cells.

It inhibits topoisomerase 1 (Top1) enzyme which participates in cellular replication and transcription.

CRLX101 also inhibits a protein called hypoxia-inducible factor-1alpha which is believed to be a master regulator of cancer cell survival mechanisms.

CRLX101, which is in Phase 2 clinical development, has been dosed in over 300 patients

AstraZeneca’s Lynparza inhibits an enzyme called poly ADP-ribose polymerase (PARP). It exploits tumour DNA repair pathway deficiencies to kill cancer cells.

Apart from ovarian cancer, AstraZeneca is investigating the full potential of Lynparza in several tumour types.

Cerulean president & CEO Christopher Guiffre said: "Preclinical data generated by AstraZeneca with the Lynparza-CRLX101 combination demonstrate the synergistic anti-tumor effect of targeting two validated pathways.

"While PARP-Top1 combos have traditionally been limited by toxicity, we believe that our NDC and the work AstraZeneca carried out to define a dose and schedule that could be taken into the clinic may allow for the Lynparza-CRLX101 combination to be delivered safely and effectively."