Dr Thomas Okarma is the President and CEO of Asterias Biotherapeutics Incorporated, a development stage biotechnology company based in California. Asterias is focusing on the commercialisation of proof of concept (POC) stage cell therapies having acquired and combined the vast expertise and patent portfolio of two regenerative medicine giants, Biotime and Geron Stem Cells.
The acquired assets include over 450 patents and patent applications, master and working cell banks, lab equipment, fully validated stem cell manufacturing facilities and clinically approved lots of Geron's GRNOPC1 oligodendrocyte progenitor cells originally developed for the treatment of CNS Disorders. Whilst applauding the enormous research and development efforts of its parent companies, Dr Okarma was keen to emphasise Asterias's resolve to learn from their mistakes.
According to Dr. Okarma, Geron spent a huge amount of time and money qualifying their source material, the H1 and H7 embryonic stem cell lines used to generate a number of their products. These cell lines were derived on mouse embryonic fibroblasts (MEFs) from donors with untraceable health histories, incurring a significant validation and regulatory burden. Asterias will use six clinical grade hESC lines for the majority of their future therapies; these have been derived under the direction of Alan Colman at the Institute of Medical Biology Singapore. These cells were derived on human feeders in cGMP compliant conditions. Asterias will use the 24,000 sq ft cGMP facility built by Geron that is fully validated and licensed for the manufacture of cells for clinical trials. Scale up will largely make use of GE wave bioreactors with cells seeded onto microcarriers for expansion. Whilst proud of the proven functionality of their products, such as embryonic stem cell derived cardiomyocytes, Asterias will be developing new strategies for manufacturing; this will include the replacement of reagents such as matrigel with poor lot-lot comparability and the optimisation of differentiation protocols using small molecules in place of expensive and variable growth factor cocktails.
In addition the company will be looking at methods to optimise cell delivery including the seeding of cells into HyStem-C a cGMP grade matrix (based on thiol-modified hyaluronan) which has been shown to improve the retention of implanted cells in a variety of indications. Adipocytes seeded in HyStem-C have recently received regulatory approval for clinical trials in Spain.
Assigning clearly defined clinical end points will be an important goal for Asterias – a challenging task in some of the targeted disease indications, particularly spinal cord injury. Dr Okarma extolled the virtues of incorporating the findings of externally validated academic and clinical institutions that utilise publically available databases such as the International Campaign for Cures of spinal cord injury Paralysis (ICCP) Clinical Guidelines Panel. This collaborative approach not only pools expertise and reduces costs, it also convinces the regulators of the unbiased validity of the chosen endpoints.
Questions from the floor were concerned with how cost of goods could be brought down in such complex manufacturing processes. Dr Okarma stated that minimising the number of manufacturing steps and increasing product purity are critical to bringing down the cost of goods. The cost of raw materials pails in comparison, an opinion echoed by speakers in later sessions.
Guest blog provided by Amelia Lane, UCL
 Alexander et al., 2009 Spinal Cord 47, 582-591