Clinical Trials

Date: 2017-06-26

Type of information: Presentation of results at a congress

phase: preclinical

Announcement: presentation of results at the International Society on Thrombosis and Haemostasis (ISTH) Meeting

Company: Catalyst Biosciences (USA - CA)

Product: CB 2679d/ISU304

Action mechanism: coagulation factor/protein.

Disease: hemophilia B

Therapeutic area: Rare diseases - Genetic diseases - Hematological diseases

Country:

Trial details:

Latest news:

• • On June 26, 2017, Catalyst Biosciences announced positive preclinical results of CB 2679d/ISU304, its next-generation coagulation Factor IX, in a well-validated preclinical model of hemophilia B. The results demonstrate the attractive pharmacokinetic and pharmacodynamic profile of CB 2679d based on bioavailability, potency, time to maximal concentration, and half-life. The Company’s Factor IX preclinical program, including the results being presented at the International Society on Thrombosis and Haemostasis (ISTH) Meeting in July 2017, supported the initiation of an ongoing Phase 1/2 proof-of-concept clinical trial evaluating CB 2679d for subcutaneous prophylaxis.
• Oral Factor IX Presentation: Pharmacokinetics and Pharmacodynamics of Daily Subcutaneously Administered CB 2679d/ISU304 In Hemophilia B Dogs.  Howard Levy, Timothy Nichols, Elizabeth Merricks, Robin Raymer, and Andrew Hetherington. The authors tested daily subcutaneous (SQ) doses of CB 2679d/ISU304 in hemophilia B dogs for six days. Factor IX antigen and activity were measured at various time points. The results are summarized as follows:
• - CB 2679d/ISU304 corrected severe hemophilia to normal in hemophilia B dogs, after six daily subcutaneous doses
• - Daily SQ dosing of CB 2679d after six doses had peak Factor IX activity levels of 60 and 53 percent at 126 hours
• - Trough activity levels 24 hours after six daily doses were 56 and 40 percent respectively
• - The progressive increase in Factor IX activity levels after daily SQ dosing of CB 2679d supported the initiation of the ongoing Phase 1/2 proof-of-concept subcutaneous dosing study in individuals with hemophilia B with the target of achieving normal Factor IX activity trough levels
• There were no emergent clinical adverse events or lab abnormalities recorded • On February 1, 2017, Catalyst Biosciences announced positive preclinical results in well-validated models of hemophilia A and B with and CB 2679d/ISU304, a next-generation coagulation Factor IX. Catalyst and its collaboration partner, ISU Abxis, plan to initiate a Phase 1/2 proof-of-concept IV/SQ clinical trial of CB 2679d/ISU304 in individuals with hemophilia B in the second quarter of 2017.
• The results, being presented in poster sessions at the European Association of Haemophilia and Allied Disorders (EAHAD) 10TH Annual Congress in Paris, France from February 1 to 3, 2017, are summarized below:
• Pharmacokinetics of Subcutaneously Administered CB 2679D/ISU304 In Minipig Compared with Benefix - Seung-Beom Hong, Howard Levy, Jae Yong Jung, Minkyung Park, A Rim Seo, and June Young Park.
• The authors administered subcutaneous doses of CB 2679d/ISU304 or BeneFIX to normal minipigs. Factor IX antigen and activity were measured at various time points. The following conclusions were made:
• - CB 2679d/ISU304 has approximately 17-times greater potency than BeneFIX and therefore can achieve higher activity at an equal mass dosing level;
• - Daily subcutaneous dosing of CB 2679d/ISU304 demonstrated the effects of the bioavailability, time to maximal concentration, and half-life by reaching a steady-state activity sufficient to correct severe hemophilia to normal, after four days of dosing;
• - There was a dose-dependent increase in plasma Factor IX antigen with subcutaneous injection of CB 2679d/ISU304; and
• - The increased potency of CB 2679d/ISU304 and pharmacokinetic results support the initiation of a Phase 1/2 subcutaneous dosing study in individuals with hemophilia B.
• Pharmacokinetics and Pharmacodynamics of Daily Subcutaneously Administered CB 2679D/ISU304 In Hemophilia B Dogs - Howard Levy, Timothy Nichols, Elizabeth Merricks, Robin Raymer, and Andrew Hetherington. The authors tested subcutaneous doses of CB 2679d/ISU304 in hemophilia B dogs. Factor IX antigen and activity were measured at various time points. The following conclusions were made:
• - Daily subcutaneous dosing of CB 2679d/ISU304 corrected severe hemophilia to normal in hemophilia B dogs, after 4 days of dosing;
• - There was a progressive increase in plasma Factor IX antigen with daily subcutaneous injection of CB 2679d/ISU304; bioavailability of CB 2679d/ISU304 was 10.3% in Hemophilia B dogs; and
• - The increased potency and pharmacokinetics of CB 2679d/ISU304 supports the initiation of the Phase 1/2 subcutaneous dosing study in individuals with hemophilia B with the objective of achieving stable normal Factor IX activity.
• • On November 14, 2016, Catalyst Biosciences announced positive results from a preclinical study of CB 2679d/ISU304 in well-validated models of hemophilia B. The study highlighted the attractive pharmacokinetic profile of CB 2679d/ISU304 based on bioavailability, potency, time to maximal concentration, and half-life, which resulted in the ability to dose CB 2679d/ISU304 subcutaneously while also achieving steady-state levels of procoagulant activity that moved hemophilia B mice from the severe range to the mild range.
• The results, being presented in a poster session at the American Society of Hematology (ASH) 58TH Annual Meeting in San Diego, Calif. from December 3 to 6, 2016, are summarized below: Pharmacokinetics of Subcutaneously Administered CB 2679d/ISU304 in Wild-Type and Hemophilia B Mice - Seung-Beom Hong, PhD, Howard Levy, MBBChir, PhD, Jae Yong Jung, MS, Minkyung Park, AS, A Rim Seo, AS, So Hyeon Seo, MS and Ed Madison, PhD. The authors tested subcutaneous doses of CB 2679d/ISU304 in both hemophilia B and wild-type mice. The wild-type mice also received subcutaneous doses of BeneFIX. Factor IX antigen and activity were measured at various time points. The following conclusions were made:
• - There was a dose-dependent increase in plasma Factor IX antigen with subcutaneous CB 2679d/ISU304;
• - The pharmacokinetic profile of CB 2679d/ISU304 was similar to BeneFIX when dosed using the same mass, however, CB 2679d/ISU304 has approximately 17-times greater potency;
• - Due to the high specific activity of CB 2679d/ISU304, a subcutaneous dose of CB 2679d/ISU304 yields much higher Factor IX activities in mouse plasma compared with the same mass dose of BeneFIX; and
• - Daily subcutaneous dosing of CB 2679d/ISU304 demonstrated the effects of the bioavailability, potency, time to maximal concentration, and half-life by reaching a steady-state activity after three days, sufficient to correct severe hemophilia to mild hemophilia in hemophilia B mice.

 

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