Cerulean Announces Clinical Collaboration with AstraZeneca and the National Cancer Institute to Evaluate the Combination of LYNPARZA™ and CRLX101

Three-Party Collaboration Will Explore Synergies Between AstraZeneca's Leading PARP Inhibitor and Cerulean's Topoisomerase Inhibitor

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Cerulean Pharma Inc. (Nasdaq: CERU) announced today that it has entered into a collaboration with AstraZeneca AB (AstraZeneca) and the National Cancer Institute (NCI), part of the National Institutes of Health, to study LYNPARZA™ (olaparib) and CRLX101. The collaboration will explore the synergistic effects of AstraZeneca's LYNPARZA, a poly ADP ribose polymerase (PARP) inhibitor, and CRLX101, Cerulean's inhibitor of topoisomerase 1 (Top1). The NCI will conduct a combination Phase I/IIa trial in the Branch led by Yves Pommier, M.D., Ph.D., Chief of the Developmental Therapeutics Branch.

"The discovery of new, therapeutic combinations that improve patient outcomes is a core part of our strategy. The combination of LYNPARZA with CRLX101 provides an opportunity to investigate the potential of LYNPARZA beyond patients with mutations in homologous repair genes such as BRCA"
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"The discovery of new, therapeutic combinations that improve patient outcomes is a core part of our strategy. The combination of LYNPARZA with CRLX101 provides an opportunity to investigate the potential of LYNPARZA beyond patients with mutations in homologous repair genes such as BRCA," said Susan Galbraith, Head of the Oncology Innovative Medicines Unit at AstraZeneca. "This is the first of several studies we will be conducting together to explore the potential of combining CRLX101 with drug candidates in our DNA damage response franchise."

"Cerulean's nanoparticle-drug conjugates, or NDCs, are suited to enable therapeutic combinations because they are designed to concentrate anti-cancer payloads inside tumor cells and spare healthy tissue," said Christopher D. T. Guiffre, Cerulean's President & Chief Executive Officer. "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."

The scientific rationale for combining PARP inhibitors with Top1 inhibitors is well understood. Simply stated, Top1 inhibitors damage DNA, and PARP inhibitors prevent DNA damage repair. CRLX101 is a Top1 inhibitor. Top1 inhibitors trap DNA-topoisomerase complexes, preventing ligation and resulting in persistent single-stranded breaks. LYNPARZA is a PARP inhibitor that exploits tumor DNA damage repair pathway deficiencies to preferentially kill cancer cells. PARP's main role is to detect and signal single-strand DNA breaks to the enzymatic complex that repairs single-strand DNA breaks.

Under this collaboration, AstraZeneca will supply LYNPARZA, Cerulean will supply CRLX101, and the NCI will fund and conduct the clinical trial under Cooperative Research and Development Agreements with the companies. The clinical trial of LYNPARZA in combination with CRLX101 in small cell lung cancer will enroll approximately 55 patients with enrollment expected to commence in the first half of 2016. For patients interested in enrolling in this clinical trial, please call NCI's toll-free number: 1-800-4-Cancer (1-800-422-6237) (TTY: 1-800-332-8615) and/or the visit: http://www.cancer.gov/.

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 I (Top1), which is involved in cellular replication and transcription, 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 300 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 LYNPARZA (olaparib)

LYNPARZA is an innovative, first-in-class oral poly ADP-ribose polymerase (PARP) inhibitor that exploits tumour DNA repair pathway deficiencies to preferentially kill cancer cells. This mode of action gives LYNPARZA the potential for activity in a range of tumour types with DNA repair deficiencies. LYNPARZA is the first PARP inhibitor to be approved for patients with germline BRCA-mutated advanced ovarian cancer, and has been launched in the U.S. and Europe. In addition to ovarian cancer, AstraZeneca is investigating the full potential of olaparib in multiple tumour types, with Phase III studies in second line gastric cancer, BRCA-mutated pancreatic cancer and adjuvant and metastatic BRCA-mutated breast cancers underway.

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 AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: www.astrazeneca.com.

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 Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission on November 16, 2015, 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.

LYNPARZA is a trademark of the AstraZeneca group of companies.

Contacts
Cerulean Pharma Inc.
Nicole P. Jones, 617-551-9606
Director, Investor Relations and Corporate Communications
[email protected]

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