Hemophilia
Hemophilia is a rare but serious bleeding disorder that results from a genetic or an acquired deficiency of a protein required for normal blood coagulation, such as factor VIII (hemophilia A) or factor IX (hemophilia B). The disease varies in severity depending on the extent of residual activity for the deficient factor that can be detected in the circulation of individual patients. Hemophilia patients suffer from both spontaneous bleeding episodes as well as substantially prolonged bleeding times upon injury that can become life threatening. In cases of severe hemophilia, spontaneous bleeding into muscles or joints is frequent and often results in permanent, disabling joint damage.
FVIIa – Wyeth
Hemophilia patients are initially treated by replacement therapy, receiving purified versions of the clotting factor for which they are deficient. However, a significant fraction of hemophilia A patients develop inhibitory antibodies against factor VIII and therefore become refractory to treatment with this factor. These inhibitor patients are then treated with recombinant human factor VIIa (rhFVIIa, NovoSeven®), an enzyme that can both initiate blood clotting and, at high doses, “bypass” the factor VIII dependent step in coagulation. However, administration of multiple doses of rhFVIIa is often required to control bleeding episodes. Sales of NovoSeven were projected to reach $1.3 B in 2009.
Catalyst has created a broad portfolio of improved rhFVIIa molecules, several of which have shown enhanced activity and longer pharmacodynamic half-life. Catalyst’s lead compound CB 813, an improved rhFVIIa for treatment of acute bleeding in hemophilia patients with inhibitors is in preclinical development. Catalyst's approach focused on the design of a molecule that combines higher clot-generating activity targeted to the site of bleeding and improved duration of action in vivo. We anticipate that both lower and fewer doses of the improved rhFVIIa will be required to control acute bleeding episodes.
Catalyst signed a worldwide exclusive licensing agreement Wyeth Pharmaceuticals on 29 June 2009. Catalyst will be responsible for discovery and research of novel FVIIa variants, including improved FVIIa proteases that may potentially allow their use in a prophylactic setting for hemophilia patients and for the control of bleeding in normal patients in a surgical or trauma setting. Wyeth will be responsible for preclinical and clinical development, manufacturing and commercialization of resulting FVIIa products.
FIX – Catalyst Biosciences
Based on the success of the improved FVIIa program Catalyst initiated a research program in late 2008 directed at improving the PK and PD properties of FIX. Catalyst has created several improved FIX proteases that are entering preclinical testing.
