The product - known as Q Cells - consists of neural stem cells called glial‐restricted progenitors (GRP) which, in healthy individuals, develop into the ‘glial cells’ that give the brain its structure and provide a support scaffolding for neurons.
Q Therapeutics claims that, when used as a therapy, GRP cells restore or preserve normal neuronal activity in patients suffering from the degenerative brain disorder ALS, which is also known as Lou Gehrig’s disease.
Manufacturing Q Cells requires isolating the GRP cells with an IgM antibody that attaches to a protein found only on the cells' surface. This antibody is then bound by a ligand conjugate enabling the cells to be collected.
US contract manufacturing organisation (CMO) Goodwin was hired to make supplies of the therapy for planned Phase I/IIa studies, which meant overcoming significant technical hurdles as spokesman David Cunningham explained.
“The initial challenge was to develop a cost effective, reproducible, and scalable manufacturing process to produce a therapeutic GMP grade monoclonal antibody that meets all critical quality attributes to be used for human use” he told us.
“Once the process to manufacture the antibody was developed, the process to conjugate the IgM: ligand was finalised utilising our extensive bioconjugation expertise” Cunningham continued.
Another major challenge was ensuring the murine hybridoma cell line used to make the IgM produced sufficient quantities of the antibody, which was only possible using perfusion instead of a fed batch culturing approach as Cunningham explained.
“While perfusion cell culture process is not unique, it demonstrates that Goodwin Biotechnology is uniquely qualified to meet the technical and regulatory challenges due to the flexibility of its platform technology.”
He added the preventing purified ‘naked’ IgM : ligand conjugate from aggregating required “buffer formulations with the appropriate additives and excipients that significantly minimized the aggregation of the purified antibody and antibody: ligand conjugate, while meeting regulatory compliance guidelines.”
“Due to the large molecular size and a low affinity to Protein A chromatography for IgM, we utilized a purification process that featured three columns” Cunningham continued.
“The process involves a mixed-mode chromatography step, followed by a capture affinity step, and ion-exchange as the polishing step. The purification process developed was scalable and GMP compliant.
“Utilizing our unique capability to develop a flexible yet GMP compliant manufacturing process that resolved the technical challenges, we were successful in scaling up the manufacturing process to produce the GMP drug product for clinical trials, and help prepare the CMC section for the IND.”
Q Therapeutics is set to commence first-in-human trials later this year for ALS, and hopes early results will show the restorative mechanism of Q-Cells may be applicable to a number of central nervous system (CNS) diseases.