Novel Therapeutics for Bleeding Disorders



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The NoT Bleeding program leverages CHOP’s international leadership in hemostasis and gene therapy research with expertise in the clinical management of patients with bleeding disorders This program functions to:

  • Conduct clinical trials in and safely integrate licensed gene therapy vectors into the clinical care of hemophilia patients and/or patients with rare bleeding disorders (RBDs)
  • Develop the next generation of novel therapeutics for bleeding disorders
    • Combine clinical and research expertise in hemostasis to identify previously unclassified bleeding disorders.

CHOP has led the development of hemophilia gene therapy through basic, translational, and clinical research efforts, thus making the NoT Bleeding program a natural extension of this longstanding work. We additionally aim for our efforts to provide a model and/or establish systems for other clinical care teams to incorporate licensed gene therapy products.

The existing basic, translational, and clinical research expertise in coagulation and gene therapy make CHOP ideally positioned to lead the clinical implementation of gene therapy as well as develop the next generation of therapeutics for bleeding disorders. Our clinical programmatic efforts will serve the basis for an expanded referral base while our research efforts have marked capacity for the development of intellectual property and grant funding.

The NoT Bleeding program also has several research objectives including

  • Repurposing current treatments for hemophilia A for select patients for hemophilia B
  • Developing monoclonal antibodies that bind and protect factor V from activated protein C (APC)-mediated inactivation and promote coagulation in the context of hemophilia or other RBDs
  • Generating novel factor VIII variants with enhanced hemostatic function for use in gene therapy and gene editing.

Preliminary data for the program was funded by grants from the Endowed Chair Funds, NIH (P01), postdoc grant from NHF, NIH/NHLBI K08 awards, Martin Villar Research program and a CHOP Cell and Gene Therapy Seed grant.

Research Highlights

  • Developing emicizumab, a medication used to treat hemophilia A, or similar bi-specific antibodies for hemophilia B therapy: Results suggest that factor VIII-mimicking bispecific antibodies may improve the bleeding in HB patients with dysfunctional FIXa/FVIIIa interactions.
  • Developing monoclonal antibodies that bind and protect FV from activated protein C (APC)-mediated inactivation and promote coagulation in hemophilia or other RBDs: Data suggest that the mAb binds FV and protects it from APC inactivation showing promise for hemophilia.
  • Rationally exploiting regulation of FVIIIa to generate enhanced hemostatic function FVIII variants for gene therapy and gene editing.