- Phase 1 results support further development of next-generation and long-acting coagulation Factor VIIa, CB 813d/PF-05280602, in patients with hemophilia A or B -
- Company made multiple presentations at the 2015 International Society on Thrombosis and Haemostasis Meeting -
SOUTH SAN FRANCISCO, Calif., June 24, 2015 (GLOBE NEWSWIRE) -- Catalyst Biosciences, Inc., a privately held biopharmaceutical company, today announced positive results from a Phase 1 clinical trial of CB 813d/PF-05280602, its next-generation and long-acting coagulation Factor VIIa. Results showed that single doses of CB 813d were well tolerated when administered to hemophilia A and B patients, and there were no instances of antibody response or thrombosis. 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 being held in Toronto, Canada from June 20 to 25, 2015.
"These results demonstrate the initial safety and pharmacologic activity of CB 813d and support further clinical development of this coagulation factor for the potential treatment of bleeding in hemophilia patients with inhibitors," said Nassim Usman, Ph.D., President and Chief Executive Officer of Catalyst. "If we can demonstrate in a larger clinical trial of longer duration that CB 813d is able to control bleeding episodes in hemophilia patients with lower and fewer doses, we would hope to someday tap the global $1.5 billion market for Factor VIIa offerings."
"A significant number of hemophilia A patients and, to a lesser extent, hemophilia B patients develop neutralizing antibodies that inactivate their first line therapies, Factor VIII and Factor IX. The short duration of action of second line therapy – typically Factor VIIa products – for these 'inhibitor' patients significantly limits the efficacy of preventative or prophylactic treatment regimens, creating one of the most acute unmet needs in the hemophilia area. Consequently, we wanted to invent and develop longer acting Factor VIIa variants that are expected to provide better therapeutic options for these patients," said Edwin Madison, Ph.D., Chief Scientific Officer of Catalyst.
Factor VIIa Phase 1 Study Design and Results
CB 813d is an improved next-generation and long-acting coagulation Factor VIIa variant and Catalyst's most advanced clinical development program. The open label, multicenter Phase 1 trial evaluated the safety and tolerability of CB 813d as well as pharmacokinetics, pharmacodynamics and coagulation ( i.e ., clot forming) activity of CB 813d when given intravenously to 25 non-bleeding hemophilia patients in single ascending dose cohorts who were then observed for up to 60 days post treatment.
Evidence of pharmacological activity was observed with dose-dependent changes in aPTT, PT, PF1+2 (prothrombin fragments 1 + 2), and TGA (thrombin generation activity). CB 813d was well tolerated across all dose groups. No treatment emergent serious adverse events were observed. There was no evidence of antibody immune or "inhibitor" response to treatment with CB 813d at days 15, 30 or 60 of the study.
Catalyst plans to initiate a clinical efficacy trial in hemophilia A and B "inhibitor" patients in 2016.
In addition to the FVIIa clinical results, Catalyst and its collaborators, also presented preclinical data at the meeting related to Catalyst's proprietary coagulation compounds, next generation variants of Factor VIIa, Factor IX, and Factor Xa.
"In our preclinical research, CB-FIX demonstrated a significantly longer duration of action in murine hemophilia B bleeding models compared with FIX products on the market and with others in development and therefore may provide hemophilia B patients with improved prophylactic therapeutic regimens," commented Dr. Madison. "Our Factor Xa preclinical research has also produced interesting lead molecules that, in murine models, exhibit both improved efficacy and safety compared with the most advanced, competing molecule."
Additional presentations are summarized below:
Factor IX: CB 2679d/ISU 304 is a next-generation coagulation Factor IX variant that is in advanced preclinical development. In an oral presentation entitled CB-FIX: an improved second generation FIX drug candidate , Madison et al . evaluated the procoagulant activity of Catalyst's Factor IX compared with existing coagulation factors such as BeneFIX® (coagulation factor IX (recombinant)) and other advanced second generation FIX variants. CB-FIX exhibited enhanced procoagulant activity, improved efficacy in inhibiting blood loss, and prolonged duration of action in bleeding and non-bleeding preclinical models. Based on these findings, CB-FIX may represent a novel second-generation FIX variant.
Factor Xa: CB-FXa is an advanced lead molecule that is in preclinical research. In an oral presentation entitled CB-FXa: an improved second generation FXa variant , Madison et al . evaluated the procoagulant activity of Catalyst's FXa variant. CB-FXa exhibited enhanced potency, greater co-factor dependence, and improved safety (in murine models) compared with various FXa proteins, including an existing clinical candidate. Based on improved in vitro and in vivo properties, CB-FXa may represent a novel second-generation FXa variant.
Factor VIIa: CB 813d/PF-05280602. Two additional Factor VIIa poster presentations were also presented and are summarized as follows:
PF-05280602, a Factor VIIa variant with enhanced in vitro potency compared to wild-type Factor VIIa in hemophilic hemostasis assays , Patel-Hett et al .
In preclinical models of hemophilia, using plasma or whole blood from hemophilia A and B patients, CB 813d exhibited enhanced potency compared with a currently marketed, wild type FVIIa in both coagulation and global hemostatic assays. This improved potency of CB 813d was similar in assays containing hemophilic plasma with or without "inhibitors".
A systems biology model for the coagulation network describes biomarker changes observed in a clinical study with FVIIa variant , Hua et al . In a translational model comparing a currently available FVIIa (Eptacog Alfa) with CB 813d, the model was able to describe dose-dependent biomarker data and to predict the role of specific kinetic rates on the enhanced potency of CB 813d.
About Hemophilia and Factor Replacement Therapy
Hemophilia, for which there is no cure, is a rare but serious bleeding disorder that results from a genetic or an acquired deficiency of a protein required for normal blood coagulation. There are two major types of hemophilia, A and B, that are caused by alterations in Factor VIII or Factor IX genes, respectively, with a corresponding deficiency in the affected proteins. The prevalence of hemophilia A and B in the United States is estimated to be around 20,000 people, with more than 400,000 cases worldwide. Hemophilia patients suffer from spontaneous bleeding episodes as well as substantially prolonged bleeding times upon injury. In cases of severe hemophilia, spontaneous bleeding into muscles or joints is frequent and often results in permanent, disabling joint damage and can become life threatening. Treatment usually involves management of acute bleeding episodes or prophylactic treatment through factor replacement therapy by infusion of patients' missing Factor VIII or IX. With the frequent infusion schedule of current therapies, adherence is difficult. In addition, convenient access to peripheral veins is often a problem, and many children require use of central venous access devices, with the concomitant risks of infection and thrombosis.
About CB 813d
CB 813d/PF-05280602, Catalyst's most advanced product candidate, is a next-generation Factor VIIa that successfully completed a Phase 1 clinical trial in February 2015 in severe hemophilia A and B with and without inhibitors. CB 813d is initially being developed for the on-demand and prophylactic treatment of severe hemophilia A and B patients with inhibitors. CB 813d was designed to combine higher clot-generating activity at the site of bleeding and improved duration of action.
About CB-FIX
CB-FIX, or CB 2679d/ISU 304, Catalyst's next most advanced product candidate, is a next-generation Factor IX that is currently in advanced preclinical development. CB-FIX is initially being developed for the on-demand and prophylactic treatment of patients with hemophilia B, a chronic disease caused by a genetic deficiency in coagulation Factor IX.
CB 2679d/ISU 304 has demonstrated enhanced duration of action in vivo in preclinical models of bleeding and coagulation correction compared with currently marketed Factor IX therapies.
About FXa Variants
Catalyst has identified Factor Xa variants that have both enhanced potency and improved safety in preclinical animal models of bleeding compared with a competing Factor Xa clinical candidate currently under development. Because Factor Xa operates late in the coagulation cascade, downstream of factors absent or nonfunctional in hemophilia, at a point where the coagulation cascade is identical in both normal and hemophiliac patients, 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 clotting activity.
About Catalyst
Catalyst is a clinical-stage biopharmaceutical company focused on creating and developing novel products based on engineered human proteases to address serious unmet medical needs in multiple high value indications. To date, Catalyst has focused its product development efforts in the fields of hemostasis, including the treatment of hemophilia and surgical bleeding, and inflammation, including prevention of delayed graft function in renal transplants and the treatment of dry age-related macular degeneration, a condition that can cause visual impairment or blindness. Catalyst's most advanced program is an improved next-generation coagulation Factor VIIa variant, CB 813d/PF-05280602, which has successfully completed a Phase 1 clinical trial in severe hemophilia A and B patients. In addition to Catalyst's lead Factor VIIa program, Catalyst has two other next-generation coagulation factors, a Factor IX variant, CB 2679d/ISU 304, that is in advanced preclinical development, and a Factor Xa variant, that is in the advanced lead stage of development. Catalyst is privately held and backed by leading venture firms including Essex Woodlands Health Ventures, HealthCare Ventures, Johnson & Johnson Innovation – JJDC, Inc., Morgenthaler Ventures, Rosetta Capital and Sofinnova Ventures. As previously announced, Catalyst has entered into a definitive agreement with Targacept, Inc. (Nasdaq: TRGT ) to merge the two companies. The merger is expected to close in the third quarter of 2015. For more information, please visit www.catbio.com .
Note Regarding Forward-Looking Statements
This press release contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statement of historical facts, included in this press release regarding our strategy, future operations, and plans are forward-looking statements. Examples of such statements include, but are not limited to, statements relating to the timing and completion of Catalyst's proposed merger with Targacept, Inc., the development, potential benefits and uses of and markets for Catalyst's product candidates and anticipated clinical trials, including timing and potential results. Actual results or events could differ materially from the plans, intentions, expectations and projections disclosed in the forward-looking statements. Various important factors could cause actual results or events to differ materially from the forward-looking statements that Catalyst makes, including the risks described in the "Risk Factors" section of the Registration Statement on Form S-4 filed by Targacept with the SEC. Catalyst does not assume any obligation to update any forward-looking statements, except as required by law.
Investors: Dr. Nassim Usman, President & CEO Catalyst Biosciences, Inc. 650.266.8674 Media: Denise Powell Red House Consulting, LLC 510.703.9491
