Hope Biosciences Licenses nuc-Gemcitabine, A ‘Trojan Horse’ Anti-nucleolin-Gemcitabine Aptamer Drug Conjugate Against Cancer

On January 13, 2017 HOPE BIOSCIENCES reported that it has acquired the exclusive rights to develop and commercialize nuc-gemcitabine (APTA-12/HOPE-888) through a licensing agreement with AptaBio Therapeutics, a Korean pharmaceutical company (Press release, Hope Biosciences, JAN 13, 2017, View Source [SID1234609541]).

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nuc-Gemcitabine consists of Antisoma’s AS1411*, a clinically-tested DNA aptamer against surface nucleolin found on many cancer cells, and dFdCMP, an activated form of gemcitabine. Unlike ADCs (antibody drug conjugates) or SMDCs (small molecule drug conjugates), which require ‘linker’ conjugation of the cytotoxic payload to the drug, nuc-gemcitabine is created by incorporating a single activated gemcitabine molecule in lieu of a thymidine molecule during the one-step solid phase synthesis of the DNA aptamer.

Clinical trials in over 80 cancer patients showed AS1411 to have modest anti-cancer activity and a favorable safety profile. nuc-Gemcitabine is 100-1,000x more potent compared to AS1411 or conventional gemcitabine (Gemzar) in pre-clinical studies. Composition of matter patent has been granted in major countries, including the United States.

"Nucleolin is constantly and abundantly expressed on the cell surface of tumor cells where it serves as a binding protein for a variety of ligands implicated in cancer growth and angiogenesis," said Dr. SungHwan Moon, President and Chief Scientific Officer of AptaBio. "High nucleolin expression is correlated with decreased survival. nuc-Gemcitabine binds to surface nucleolin with high specificity and affinity, leading to internalization of the aptamer-drug into tumor cells, where it mediates cell death. We have demonstrated significantly greater anti-cancer activity at low doses of nuc-gemcitabine containing the equivalent of 3 mg/kg gemcitabine versus 80-100 mg/kg of Gemzar in gemcitabine-resistant pancreatic cancer xenograft mouse models."

"HOPE-888 has demonstrated impressive anti-cancer activity in preclinical models. It could truly be a game changing treatment strategy for pancreatic cancer and other difficult-to-treat malignancies," said George Uy, CEO and Founder of HOPE. "Our goal is to file IND application in the next 12-18 months and bring it into the clinic soon thereafter. We intend to truly personalize nuc-gemcitabine therapy by screening patients for nucleolin-expression with a biomarker kit."