Geron Corporation, CXR Biosciences Ltd and the Roslin Institute announced a collaboration to develop and commercialize human embryonic stem cell (hESC)-derived hepatocytes for use in in vitro assays of drug metabolism and toxicity.

Under the terms of the agreement, Geron, the Roslin Institute and CXR will collaborate to develop enhanced protocols for efficient, scalable and cost-effective derivation of hepatocytes from hESCs, to characterize their use for the metabolic and toxicological profiling of drugs in development, and to format them into in vitro assays suitable for high-throughput screening applications.

Geron will bring to the partnership: i) its existing hES cell lines, ii) extensive intellectual property and know-how in the hESC field, and iii) its issued patents for hepatocytes derived from hESCs and their use in drug screening. The Roslin Institute will utilize its expertise in hESC culture and gene reporter assays, and produce hESC-derived hepatocytes under funding from Geron. CXR will contribute its expertise in hepatocyte cell culture, as well as its proprietary metabolic and reporter construct-based assays for hepatocyte function. Geron and CXR will commercialize the resulting products. Other financial terms of the agreement were not disclosed.

Sourcing of human hepatocytes for in vitro assays has long been a key problem in pharmaceutical drug development. Primary human hepatocytes have traditionally been sourced from cadavers or cancer resections, but supply of these cells is limited and phenotypes vary widely among the sourced donors. Because primary hepatocytes cannot be sustained in culture without losing function, their availability is dependant on repetitive sourcing, creating supply constraints and further contributing to assay variability.

Hence, pharmaceutical companies have had to rely heavily on animal models for preclinical metabolism and toxicity testing, which are often not predictive for man. The expensive and low-throughput nature of animal models has forced such testing to be reserved for compounds in late preclinical development, requiring pharmaceutical companies to invest significant resources in compounds before their metabolism and toxicity profiles are known, which contributes to their high failure rates in late preclinical testing.

Geron's hESC-derived hepatocyte technology presents a unique opportunity to address this bottleneck in drug discovery by providing standardized hepatocyte lines that are predictive of human metabolism and toxicology. Undifferentiated hESCs maintain pluripotency and stable karyotypes after years in culture, providing a virtually limitless supply of uniform source material.

Development of feeder-free and serum-free growth conditions for hESCs enable the economically viable, scalable production of commercial quantities of these cells. Geron has successfully demonstrated in vitro derivation of human hepatocytes that express drug metabolizing enzymes from hESCs. In this collaboration, the partners will develop enhanced protocols to improve yields and maturity of hESC-derived hepatocytes, and will format the resulting cells into commercially useful high-throughput assays for drug metabolism and toxicity.