GLASGOW, U.K.— A landmark,multinational, collaborative stem-cell research project led by Belgium-basedbiotech TiGenix recently gained a new partner in Sistemic, a provider ofmiRNA-based products to the drug development, cell therapy and bioprocessingmarkets.
The project, called REGENER-AR, aims to progress TiGenix'sCx611 stem cell therapy for rheumatoid arthritis through early clinical trials.The multidisciplinary consortium spans several countries—Belgium, Spain,France, the Netherlands and now the U.K.—and has been granted $7.8 million fromthe European Seventh Framework Programme (FP7) under the topic "Regenerativemedicine clinical trials" within the FP7's Health theme.
TiGenix is almost as new as the consortium itself, as thecompany merged with Cellerix, a Spanish biotech that is also focused on celltherapies, a little more than a year ago. Since that time, the newly formedcompany has been working to evaluate adipose tissue-derived stem cell (eASC)therapies for autoimmune and inflammatory diseases like rheumatoid arthritis(RA).
Cx611 is an allogeneic eASC product candidate for thetreatment of rheumatoid arthritis and is currently being investigated in aPhase IIa trial. The trial is based on a three-step dose-finding protocol,where each step starts with a safety review of the first three patients after40 days of dosing. InFebruary, the study opened the third and last cohort.
The study has three objectives. Its primary objective todetermine safety, feasibility and tolerance, and to identify dose-limitingtoxicity and the dose for future clinical trials on efficacy of the intravenousinfusion of allogeneic eASCs for patients suffering rheumatoid arthritis undertreatment with at least two non-biologic-DMARDs who have previously failed totreatment with at least two biologics. The secondary objective is to obtaininformation on the clinical and functional effects of the intravenous infusionof allogeneic eASCs cells in patients with rheumatoid arthritis, and the third objectiveis to explore pharmacodynamic parameters.
The multicenter study involves 53 patients divided intothree cohorts with different dose regimens and with the same administration regimensand is being conducted in more than 20 Spanish centers. TiGenix expects toreport the final results of the Phase IIa in the first half of 2013. If theresults are as anticipated, TiGenix plans to take the program forward in one orseveral inflammatory and autoimmuneorphan or niche indications.
"Our role will be the clinical coordination of clinicaltrials within the grant, and then we will have a series of leading roles in thepreclinical evaluation of Cx611," says Wilfried Dalemans, chief technologyofficer and vice president of regulatory affairs at TiGenix. "The goal of this projectis to progress a treatment for RA, which is a complex disease. It would begreat if we have supporting clinical data which indicate that stem cells canindeed be a possible treatment option for RA patients. On the preclinical side,a more in-depth understanding of the mode of action of stem cells incontrolling inflammation will be equally important."
The consortium has 10 partners to date, and the most recentaddition to that group is Sistemic, which will use its miRNA-based screeningplatform to provide identity markers for TiGenix's product. This miRNA-basedfingerprint will then be developed to fully characterize the product in linewith regulatory requirements and provide a quality control (QC) tool to monitorproduct quality during manufacturing scale-up for subsequent clinical trialsand aid in the selection of manufacturing process improvements.
"Stem cells are still in the early stages of their science,"Dalemans notes, "and although we know they have great potential in inflammatorycontrol and tissues, there are still a lot of unknowns with respect to theirorigin and genealogy. One aspect of miRNAs is to focus on regulatory pathwaysthat can group types of regulatory pathways within cells. Sistemic has built atechnical platform based on the scientific background of miRNAs, so they werethe partner of choice."
miRNA-based characterization provides a powerful andinformative way to identify and monitor the identity, purity, safety anddifferentiation staging of stem cells, says Vincent O'Brien, chief scientific officerat Sistemic.
"Importantly, this approach not only gives a succinct readout on the status of the cells, but also provides insight into the underlyingbiological effects associated with any change observed," says O'Brien. "We seemiRNAs acting as molecular beacons on the molecular status of the cell system,providing a much less cumbersome, more robust and biologically informative toolto monitor cells."
miRNA-based characterization holds enormous promise forcell-therapy product development because current methodologies are time- andlabor-intensive and are becoming a bottleneck in progressing cell therapiesthrough to manufacturing, says Verna McErlane, Sistemic's director ofcommercial operations.
"Full characterization is the cornerstone to successfuldevelopment of any cell therapy and must span from early R&D through pilotproduction for trials to full-scale manufacture," says McErlane. "Only in thisway can a cell product be produced consistently and reproducibly. As aconsequence, innovative companies such as Sistemic are working on novelmethodologies, tool and products that can be used to sensitively and robustlycharacterize cell therapy products. In essence, sophisticated molecularcharacterization, and the ability to link this back to system biology, will beinstrumental in delivering full characterization of the cell, the process andthe product. As with any new technology it will be important that they arestandardized for use in the industrial setting—something that Sistemic isdeveloping in collaboration with its global partners."