Cobra, Kahr Extend Fusion Protein Development and Manufacturing Alliance
CMO will generate cell-line and process development for GMP production of dual-targeting proteins.!--h2>
Cobra Biologics will carry out cell-line and process development of Israeli firm Kahr Medical’s two lead fusion Signal Converter Protein (SCP) candidates KAHR-101 and KAHR-102, for future preclinical and clinical testing. The fusion proteins are in preclinical development for the treatment of cancer and autoimmune disorders. The new contract extends a prior partnership between the firms through which Cobra generated an initial CHO production cell line and developed a production and purification process for the candidates. Cobra will now expand these activities through its maxXpress service for clone selection and production, and carry out process development and scale-up for GMP production.
KAHR-101 and KAHR-102 are the lead molecules to emerge from Kahr’s SCP platform. The technology effectively generates fusion proteins with two functional ends that target different ligands or receptors, to either effect or prevent signaling between two target cells, or modulate cross-talk between two receptors on the same cell.
Both KAHR-101 and KAHR-102 are expected to start in clinical development in 2013. KAHR-101 is a fusion-protein that links two membrane proteins: Fn14 (the receptor for the proinflammatory cytokine Tweak) and TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), both of which are implicated in immunity and cancer. The Fn14 component of KAHR-101 binds to Tweak and blocks the ligand from activating the stimulatory Fn14 receptor found on the surface of T-cells and cancer cells. The TRAIL component binds to TRAIL receptors on activated T-cells or cancer cells. In effect, the firm claims, KAHR-101 not only inhibits target cell proliferation by blocking Tweak, but also converts the activating signal into a command that triggers T-cell or cancer apoptosis. The candidate is initially in development as a potential treatment for multiple sclerosis, and clinical trials are projected to start in 2013.
KAHR-102 is a fusion protein that links the immune- and cancer-related membrane proteins, CTLA-4 and FasL. The CTLA-4 component of KAHR-102 binds to B7 co-stimulators on antigen-presenting-cells and blocks them from engaging their cognate stimulatory CD28 receptor on T cells. The FasL component of KAHR-102 binds to its cognate Fas receptor, which is upregulated on activated T cells, and triggers apoptosis. Kahr claims the net effect of combining these blocking and triggering functions is to convert a T cell activating signal into an inhibitory signal.