ONZEALD™ (etirinotecan pegol)
(formerly NKTR-102)

Therapeutic Area Nektar
Indication Phase Partner
ONZEALD™ (etirinotecan pegol)
Advanced Breast Cancer and Brain Metastases
To be filed for Conditional Approval in the EU - June 2016
Daiichi Sankyo
Advanced Breast Cancer and Brain Metastases
Phase 3 in US

ONZEALD™ (etirinotecan pegol) Clinical Data and Product Profile

ONZEALD (etirinotecan pegol) is the first long-acting topoisomerase I-inhibitor (Topo I) designed to concentrate in tumor tissue, provide sustained tumor suppression throughout the entire chemotherapy cycle, and to reduce the peak exposures that are associated with toxicities of other cytotoxics. ONZEALD was invented by Nektar using its advanced polymer conjugate technology platform, and is the first oncology product candidate to leverage Nektar's releasable polymer technology platform.

Topo I-inhibitors are important chemotherapeutic agents used to treat cancer. Immediately after dosing, however, standard topo I-inhibitors reach high peak concentrations and diffuse quickly throughout the body — penetrating and damaging healthy tissue, such as bone marrow, as well as tumor tissue. Subsequent rapid metabolism limits topo I exposure in tumor cells, reducing the duration of their effect and resulting in a much lower tumor exposure to the active metabolite that may limit their efficacy.

ONZEALD is a novel chemotherapeutic designed to enhance the anti-cancer effects of topo I-inhibition while minimizing its toxicities. Unlike first generation topo I-inhibitors that exhibit a high initial peak concentration and short half-life, ONZEALD's unique pro-drug design results in a lowered initial peak concentration of active topo I inhibitor in the blood. The large ONZEALD molecule is inactive when administered. Over time, the body's natural enzymatic processes slowly metabolize the linkers within the molecule, continuously freeing active drug that then works to stop tumor cell division through inhibition of topo I.

Clinical and preclinical studies have shown that the half-life of active drug generated from ONZEALD is greatly extended to 50 days (compared to 48 hours for irinotecan) and that active drug remains in circulation throughout the entire chemotherapy cycle, providing sustained exposure to topo I inhibition. In preclinical models, ONZEALD achieved a 300-fold increase in tumor concentration as compared to a first generation topo I-inhibitor. Because ONZEALD is a large molecule, it is believed to penetrate the leaky vasculature within the tumor environment more readily than normal vasculature, concentrating and trapping ONZEALD in tumor tissue. ONZEALD has been evaluated in breast, ovarian, colorectal, brain and lung cancer.

BEACON Phase 3 Data:

Data from the BEACON study, a Phase 3 clinical study of etirinotecan pegol in metastatic breast cancer were published in the November 2015 issue of The Lancet Oncology (click here to view manuscript) These data were previously presented at the 2015 ASCO Annual meeting (click here to download this presentation).

February 14, 2016 26.2 with Donna - Breast Cancer Marathon Jacksonville, FL
April 16-20, 2016 AACR Annual Meeting 2016 New Orleans, LA
June 3-9, 2016 2016 ASCO Annual Meeting Chicago, IL
December 6-10, 2016 San Antonio Breast Cancer Symposium San Antonio, TX

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