Stopping bleeding is good – preventing bleeding is better

All currently approved medicines for hemophilia are injected into a patient’s veins – at Catalyst, we believe that a clotting factor that could instead be injected just under the skin would enhance the treatment, and lives, of patients with hemophilia.

Catalyst is focused on the prevention of spontaneous bleeding in hemophilia, even during surgery, using our potent, coagulation factors to promote blood clotting. We plan to initiate two clinical trials in 2017, one in patients with Hemophilia B using our next-generation Factor IX, CB 2679d, and the other in hemophilia inhibitor patients using our next-generation Factor VIIa, marzeptacog alfa (activated) (formerly known as CB 813d).

Hemophilia is a rare but serious bleeding disorder

Hemophilia patients suffer from spontaneous bleeding episodes and substantially prolonged bleeding times that can become limb- or life-threatening following injury or trauma. In cases of severe hemophilia, spontaneous bleeding into muscles or joints is frequent and often results in permanent, disabling joint damage. Hemophilia results from a genetic or acquired deficiency of a protein required for normal blood coagulation.

Hemophilia patients are currently treated with replacement therapy of key coagulation proteins, Factor VIII for Hemophilia A or Factor IX for Hemophilia B.  A complication for hemophilia patients receiving factor replacement therapy is the production of antibodies against the replacement factor, also called inhibitors. The overall prevalence of inhibitor formation is up to 30% in patients with hemophilia A and up to 5% in patients with hemophilia B.

Inhibitor patients are treated with what are known as “bypass” agents that initiate coagulation by a pathway that is independent of Factor VIII or Factor IX.  There are currently two approved “bypass agents”, Factor VIIa (for example NovoSeven™) and FEIBA™.  However, current hemophilia drugs for patients with inhibitors have significant limitations regarding potency, duration of action and often require frequent dosing – and they are all injected intravenously which is not ideal for patients who predominantly take these medicines at home.

We believe that the shortcomings of currently approved therapies are barriers to prophylactic treatment strategies that, if surmounted, could provide meaningfully improved long-term clinical outcomes for patients. Catalyst's engineered proteases in the fields of hemostasis are designed to overcome the significant limitations of current treatment options, facilitate preventative treatment, and ultimately deliver substantially better outcomes for patients.

Factor IX

Catalyst created a portfolio of improved Factor IX proteases, including the clinical development candidate CB 2679d for treatment of hemophilia B, a life-long disease caused by a genetic deficiency in coagulation Factor IX.

The leading recombinant human Factor IX on the market for treating acute bleeding episodes in hemophilia B patients has a short half-life and is therefore not ideal for prophylactic treatment.

CB 2679d has shown significantly higher potency in pre-clinical studies versus other FIX products on the market and in development. Based on data from well-validated animal models of hemophilia, CB 2679d may provide hemophilia B patients with a viable subcutaneous prophylactic therapy.

Catalyst has a collaboration with ISU Abxis to advance the development of CB 2679d through Phase 1/2 proof-of-concept study in hemophilia B patients. After Phase 1, ISU Abxis retains exclusive commercial rights in Korea while Catalyst retains full development and commercial rights for CB 2679d outside of Korea.

Factor VIIa

Marzeptacog alfa (activated) (formerly known as CB 813d) is a next-generation Factor VIIa that was designed to allow for the effective, long-term, prophylaxis in hemophilia patients with inhibitors. Catalyst has successfully completed an intravenous Phase 1 clinical trial in patients with severe hemophilia A and B with and without inhibitors.

Catalyst designed marzeptacog alfa  (activated) (formerly known as CB 813d) to combine higher clot-generating activity at the site of bleeding and improved efficacy. Catalyst anticipates that this product candidate could be used for subcutaneous prophylactic treatment.

Positive results from an open label, multicenter Phase 1 intravenous dosing clinical trial of marzeptacog alfa (activated) (formerly known as CB 813d) were reported in June 2015. Marzeptacog alfa  (activated) (formerly known as CB 813d) was given intravenously to 25 non-bleeding hemophilia patients in single ascending dose cohorts who were then observed for up to 60 days post treatment. Results showed that single doses of marzeptacog alfa (activated) (formerly known as CB 813d) were well tolerated when administered to hemophilia A and B patients, and there were no instances of antibody response or thrombosis. Marzeptacog alfa (activated) (formerly known as CB 813d) demonstrated pharmacological efficacy as measured by significant shortening of aPTT (activated partial thromboplastin time) and PT (prothrombin time) for up to 48 hours post dosing. The results were presented in a poster session at the International Society on Thrombosis and Haemostasis (ISTH) Meeting in June 2015.

Factor Xa

Catalyst has identified Factor Xa variants that have enhanced potency, improved safety, and superior duration of action in preclinical models of bleeding compared with a competing Factor Xa in clinical development. Catalyst believes that a safe and effective Factor Xa product has the potential to be used both to treat hemophilia patients and to reduce blood loss in trauma and surgery in patients with normal coagulation systems and clotting activity or those who are taking anti-platelet agents or anticoagulants.

Catalyst’s FXa program has reached the lead candidate stage of research and is available for partnering.