dalcinonacog alfa (CB2679d) / ISU Abxis, GC Biopharma - LARVOL DELTA

Model-Informed Support of Dose Selection for Prophylactic Treatment with Dalcinonacog Alfa in Adult and Paediatric Hemophilia B Patients. (PubMed, Adv Ther) - P1, P2b | "This study supported the adult dose selection for DalcA in the presence of sparse data and enabled first-in-paediatric dose selection to achieve FIX levels that reduce risk of spontaneous bleeds."

Journal • Hematological Disorders • Hemophilia • Pediatrics • Rare Diseases

Using Recombinant Adeno-Associated Viral Vectors for Long-Term Expression of a Hyperactive Human Factor IX Mutant in Hemophilic Mice and Comparison of AAV-LK03 and AAV-KP1 in Nonhuman Primates (ASGCT 2022) - "Our study demonstrates that combining a next generation AAV vector with the potency enhanced FIX variant CB 2679d-GT has the potential to improve transgene expression and effectively lower the viral dose needed to achieve therapeutically relevant FIX activity levels when administered systemically. This would substantially reduce the cost of rAAV based FIX gene therapy, the potential for liver toxicity and the risk of adverse immune responses with high doses."

Preclinical • Gene Therapies • Hematological Disorders • Hemophilia • Hepatology • Rare Diseases • APOE

Form 10-Q Catalyst Biosciences, Inc. (U.S. Securities and Exchange Commission) - "...We have received guidance from the FDA on the design of the registrational Phase 3 clinical trial and the necessary data to support its initiation and are actively seeking a partner for this program. We are exploring opportunities to license or sell DalcA to another party for further development."

FDA event • Licensing / partnership • Genetic Disorders • Hemophilia

CATALYST BIOSCIENCES : Management’s Discussion and Analysis of Financial Condition and Results of Operations (form 10-Q) (Market Screener) - "Recent Development Program Updates....The Phase 3 registration trial - MAA-304 ('Crimson 1')...We plan to submit our first report to the Data and Safety Monitoring Board ('DSMB') in 2021. We are also enrolling patients in a Phase 1/2 trial ('MAA-202') of MarzAA for treatment of bleeding in Factor VII Deficiency, Glanzmann Thrombasthenia, and in individuals with HA with inhibitors treated with Hemlibra...DalcA...We are planning to meet with the FDA to discuss the design of a registrational Phase 3 clinical trial and the necessary data to support its initiation and are actively seeking a partner for this program."

DSMB • FDA event • Genetic Disorders • Hemophilia

[VIRTUAL] Mitigation of Injection Site Reactions after Subcutaneous Administration of Dalcinonacog Alfa (DalcA) in Hemophilia B Using Preclinical Models (ISTH 2021) - "Background : Prophylactic subcutaneous (SQ) administration of dalcinonacog alfa (DalcA), an engineered recombinant factor IX (FIX) variant with 22-fold enhanced potency compared with BeneFIX, provides stable and protective therapeutic FIX levels in individuals with Hemophilia B. Phase 1 and 2b studies demonstrated DalcA was well tolerated and efficacious, showing sustained FIX levels and no bleeding events from therapy start through washout. A biomarker signature predictive of minipig ISR was generated from the cross comparison of cutaneous proteomes of minipig and ex vivo human skin models. Conclusions : This approach of integrating ex vivo and in vitro studies with a defined biomarker signature coupled with a drug product stability profile facilitated identification of an improved formulation buffer expected to lower the risk of clinical ISR with SQ DalcA injection without impacting DalcA product quality."

Preclinical • Dermatology • Hematological Disorders • Hemophilia • Immunology • Inflammation • Pain • Rare Diseases

Catalyst Biosciences Announces Presentations at the International Society on Thrombosis and Haemostasis (GlobeNewswire) - "Catalyst Biosciences...announced four poster presentations on marzaptacog alfa (activated) (MarzAA) and dalcinanonog alfa (DalcA) at the upcoming International Society on Thrombosis and Haemostatis (ISTH) Virtual Congress being held from July 17-21, 2021."

Clinical protocol • Preclinical • Hemophilia

Efficacy and safety of subcutaneous prophylaxis with dalcinonacog alfa in adults with haemophilia B. (PubMed, Haemophilia) - "Subcutaneous dalcinonacog alfa is effective in raising FIX levels into the mild haemophilia range, comparable to intravenous extended half-life FIX clotting factors."

Clinical • Journal • Hematological Disorders • Hemophilia • Pain • Rare Diseases

Catalyst Biosciences Announces Publication of CB 2679d Preclinical FIX Gene Therapy Data in Blood, the Journal of the American Society of Hematology (GlobeNewswire) - "Catalyst Biosciences, Inc. (NASDAQ: CBIO) today announced the publication of preclinical data from its study of CB 2679d-GT in Hemophilia B mice in Blood, the peer-reviewed, official journal of the American Society of Hematology. The paper...demonstrated superiority of the Company's CB 2679d-GT gene therapy candidate over that of the R338L-Padua variant, which is currently used in clinical trials."

Preclinical • Hemophilia

Gene Therapy For Hemophilia B Using CB 2679d-GT: A Novel Factor IX Variant With Higher Potency Than Factor IX Padua. (PubMed, Blood) - "FIX expression was sustained for at least 20 weeks with both CB 2679d-GT and R338L-Padua while immunogenicity was not significantly increased. This is a novel gene therapy study demonstrating the superiority of CB 2679d-GT highlighting its potential to obtain higher FIX activity levels and superior hemostatic efficacy following AAV directed gene therapy in hemophilia B patients than what is currently achievable with the R338L-Padua variant."

Journal • Gene Therapies • Hematological Disorders • Hemophilia • Hepatology • Immunology • Inflammation • Rare Diseases

Safety, Pharmacokinetics and Pharmacodynamics of a Next-Generation Subcutaneously Administered Coagulation Factor IX Variant, Dalcinonacog Alfa, in Previously Treated Hemophilia B Patients. (PubMed, J Thromb Haemost) - P1 | "The data demonstrated that DalcA achieved protective FIX activity levels between 11-18%, corresponding to a reduced chance of spontaneous bleeds. Based on the results, a Phase 2b trial to assess the safety and efficacy of 28 daily SQ doses of DalcA was performed."

Clinical • Journal • PK/PD data • Hematological Disorders • Hemophilia • Rare Diseases

Catalyst Biosciences Hosting Research & Development Call on Systemic Complement Regulator Programs (GlobeNewswire) - "Catalyst Biosciences, Inc....today announced that it will host a research and development call on the Company’s systemic complement regulator programs on Monday, December 14, 2020 at 12:00 pm Eastern Time. Members of Catalyst Biosciences’ management team will provide an overview of the Company’s complement programs, including disclosure of the Company’s first subcutaneously-dosed systemic complement development candidate."

Live event • Review • Genetic Disorders • Hemophilia

Dose-escalation Study to Investigate the Safety, PK, and PD of ISU304/CB2679d in Hemophilia B Patients (clinicaltrials.gov) - P1; N=11; Completed; Sponsor: ISU Abxis Co., Ltd.; N=16 ➔ 11

Clinical • Enrollment change • Hematological Disorders • Hemophilia • Rare Diseases

ISU Abgis' partner US catalyst publishes a new hemophilia drug 'DalcA' in the famous academic journal Flos One [Google translation] (Maekyung Media Group) - "Isu Abzis has recently published a paper on preclinical trials of 'Dalcinonacog Alfa (ISU304)'...It was announced on the 3rd that it was published on (Plos One). The theme of this paper is 'preclinical evaluation of the next generation coagulation factor IX variant administered subcutaneously, Dalcinonacog Alfa', containing the preclinical results of testing pharmacodynamics, pharmacokinetics, and safety after administration of DalcA to a dog with hemophilia B....'The data...can provide a more effective and convenient treatment than the current intravenous rFIX product.'"

Preclinical • Hemophilia

Activity measurements of dalcinonacog alfa. (PubMed, Haemophilia) - "Within and between assay method discrepancy was found when assaying dalcinonacog alfa. Methods for potency labelling and clinical monitoring should be given careful consideration."

Journal • Hematological Disorders • Hemophilia • Rare Diseases

Preclinical evaluation of a next-generation, subcutaneously administered, coagulation factor IX variant, dalcinonacog alfa. (PubMed, PLoS One) - "The increased potency of dalcinonacog alfa facilitated the initiation and completion of the Phase 1/2 subcutaneous dosing study in individuals with hemophilia B."

Journal • Preclinical • Hematological Disorders • Hemophilia • Rare Diseases • Thrombosis

The time has come to show the true value of ISU Abzis [Google translation] (Global Economics) - "In addition, phase 2 clinical trials for ISU304, a hemophilia B treatment drug, were completed in June, and milestones are expected to be received by entering phase 3 clinical trials in the first half of 2021."

New P3 trial • Trial completion • Hemophilia

[VIRTUAL] Thrombin Generation Potential of Modified FIX: Dalcinonacog Alfa (ISTH 2020) - " Thrombin generation profiles (Thrombinoscope, Stago) of DalcA (Catalyst Biosciences), RB (Benefix, Pfizer) and PD (14/148, NIBSC) were compared at 3 concentrations: 0.01, 0.05 and 0.3 International Unit (IU)/ml, based on labelled potency, using 3 different stimuli: high tissue factor (TF) (~1pM), low TF (~0.1pM) and FXIa (6.5 mIU FXIa/ml + 0.05pM TF), each containing phospholipid (4µM). On the same IU basis, DalcA had higher thrombin generation potential than RB and PD FIX and this may be due to the modifications in DalcA which enhance its binding to FVIIIa and reduced its inhibition by antithrombin. This may translate to better efficacy in vivo."

F2

Catalyst Biosciences Announces Closing of Public Offering of Common Stock (GlobeNewswire) - "Catalyst Biosciences, Inc....today announced the closing of an underwritten public offering of 4,615,384 shares of its common stock, offered at a price of $6.50 per share to the public....Catalyst anticipates using the net proceeds from this offering for general corporate purposes, which may include research and development activities in its complement program, clinical and manufacturing activities for marzeptacog alfa and dalcinonacog alfa..."

Financing • Hemophilia

Catalyst Biosciences Announces Proposed Public Offering of Common Stock (GlobeNewswire) - "Catalyst Biosciences, Inc....today announced that it is offering shares of its common stock in an underwritten public offering....Catalyst anticipates using the net proceeds from this offering for general corporate purposes, which may include research and development activities in its complement program, clinical and manufacturing activities for marzeptacog alfa and dalcinonacog alfa..."

Financing • Hemophilia

Catalyst Biosciences presents positive final data from its phase 2b trial of subcutaneous dalcinonacog alfa (DalcA) at the World Federation of Hemophilia virtual summit 2020 (Catalyst Biosciences Press Release) - P2b, N=6; NCT03995784; Sponsor: Catalyst Biosciences; "Catalyst Biosciences, Inc....today announced final efficacy and safety data from its Phase 2b trial of DalcA...for the treatment of Hemophilia B. The poster was presented at the World Foundation of Hemophilia Virtual Summit, taking place from June 14 -19, 2020....The poster, entitled: 'Phase 2b Trial to evaluate the safety and factor IX levels of a daily subcutaneous prophylaxis treatment regimen of dalcinonacog alfa in Hemophilia B' presented by Howard Levy, M.B.B.Ch., Ph.D., M.M.M., chief medical officer, Catalyst Biosciences highlights results from the study....'The trial data showed excellent efficacy and a clean safety profile, all subjects achieved steady state FIX activity levels exceeding the primary endpoint of 12%.' "

P2b data • Hemophilia

[VIRTUAL] Phase 2B Trial to evaluate the safety and factor IX levels of a daily subcutaneous prophylaxis treatment regimen of dalcinonacog alfa in hemophilia B (WFH 2020) - "Interim data show that the primary endpoint has been met. No ADAs were detected. The extended half-life may allow for less frequent dosing after steady-state levels have been achieved."

Clinical • P2b data • Gene Therapies • Hematological Disorders • Hemophilia • Rare Diseases

Catalyst Biosciences announces oral and poster presentations at the World Federation of Hemophilia Virtual Summit 2020 (Catalyst Biosciences Press Release) - "Catalyst Biosciences, Inc....today announced oral and poster presentations at the upcoming World Foundation of Hemophilia Virtual Summit, taking place from June 14-19, 2020....The open-label Phase 2b study of dalcinonacog alfa (DalcA), a next-generation subcutaneously (SQ) administered Factor IX (FIX) for the treatment of hemophilia B was designed to evaluate daily SQ dosing and the ability to maintain protective steady state FIX levels above 12% in six individuals with severe hemophilia B....Dr. Blouse will present data from preclinical studies of Catalyst’s hemophilia B gene therapy CB 2679d-GT..."

P2b data • Preclinical • Hemophilia

Catalyst Biosciences reports first quarter 2020 operating & financial results and provides a corporate update (BioSpace) - "MarzAA: Report final data in the second quarter of 2020 from a MarzAA Phase 1 pharmacokinetic and pharmacodynamic study...Initiate a Phase 3 open-label trial in 2020, evaluating the efficacy of SQ MarzAA to treat episodic bleeding in individuals with hemophilia A or B with inhibitors...DalcAA: Report final Phase 2b trial data in the second quarter of 2020....CB 2679d-GT (FIX Gene Therapy): Report initial non-human primate data in the second quarter of 2020."

New P3 trial • P1 data • P2b data • Preclinical • Genetic Disorders • Hemophilia

Catalyst Biosciences announces oral presentation at the World Federation of Hemophilia 2018 World Congress (Catalyst Biosciences Press Release) - “Catalyst Biosciences…today announced an oral presentation of clinical safety data from the Phase 1/2 study of subcutaneously-administered, prophylactic Factor IX candidate CB 2679d for the treatment of hemophilia B at the World Federation of Hemophilia (WFH) 2018 World Congress being held May 20-24, 2018 in Glasgow, Scotland.”

P1/2 data • Genetic Disorders • Hemophilia

Catalyst’s CB 2679d was shown to outperform BeneFix in phase 1/2 trial in hemophilia B (Hemophilia News Today) - P1/2, N=12; NCT03186677; "The first results showed that CB 2679d could induce a 22 times more potent response than that observed with BeneFix. In addition, the new recombinant clotting factor demonstrated an improved stability, remaining in circulation in the body longer than BeneFix....More preliminary top-line results of the trial are expected by the end of 2017. The trial is expected to be completed in early 2018."

P1/2 data • Trial completion • Genetic Disorders • Hemophilia