Selexys Pharmaceuticals is developing a humanized monoclonal antibody drug directed against P-selectin for the treatment of vasoocclusive crisis in patients with sickle cell disease. P-selectin mediates the first step in the recruitment of white blood cells to sites of inflammation. Vasoocclusion is precipitated by a P- selectin-mediated adhesion of sickled red cells and leukocytes. These cells bind to and block blood vessels precipitating painful crises, a hallmark of the disease. In preclinical studies in sickle cell models, administration of an antibody to P-selectin prevents vasoocclusion. The major aims of this proposal are the development of pharmacokinetic, pharmacodynamic, and immunogenicity assays to support an animal toxicology study and a Phase I/II trial in patients with sickle cell disease. In Phase 1 of this Fast Track Proposal, an ex vivo pharmacodynamic (PD) assay will be developed to measure the ability of a humanized antibody to P-selectin to block adhesion of monocytes to activated platelets using human/primate serum. The assay will allow us to establish a surrogate marker of drug activity. A pharmacokinetic (PK) ELISA based assay will be developed to measure the concentration of the humanized antibody in blood. This assay will allow us to monitor blood levels of the P-selectin antibody in primate and human studies. An immunogenicity assay will be developed to monitor the formation of human anti-humanized antibodies (HAHA) in human clinical studies. A primate safety/toxicity study will be conducted in a dose ranging study in cynomolgus monkey (Macaca fascicularis) to assess safety, toxicity, PK, PD of the humanized anti-P selectin antibody. In Phase 2 of this proposal a Phase I/II clinical study will be conducted in sickle cell patients to assess safety and the PK, PD and immunogenicity of a humanized antibody to P-selectin. The primary goal of the proposed study is to characterize the antibody prior to commencing a Phase II chronic dosing trial. The overarching goal of our program is to develop and commercialize a humanized antibody to P-selectin to treat vasoocclusive crisis in sickle cell patients. In doing so we are addressing a critical unmet medical need for a rare, debilitating orphan disease which currently has no effective approved treatment.

Public Health Relevance

This proposal supports development of a humanized antibody to P-selectin to treat vasoocclusive crisis in sickle cell patients. Sickle cell disease is an inherited blood disorder that affects over 70,000 persons, primarily African-Americans, in the U.S. The drug being developed addresses a critical unmet medical need for a rare, debilitating orphan disease which currently lacks an effective treatment.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
1R44HL093893-01A1
Application #
7612577
Study Section
Special Emphasis Panel (ZRG1-CVS-K (10))
Program Officer
Qasba, Pankaj
Project Start
2009-06-01
Project End
2011-05-31
Budget Start
2009-06-01
Budget End
2010-05-31
Support Year
1
Fiscal Year
2009
Total Cost
$1,251,579
Indirect Cost
Name
Selexys Pharmaceuticals Corporation
Department
Type
DUNS #
145737131
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104
Ataga, Kenneth I; Kutlar, Abdullah; Kanter, Julie et al. (2017) Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease. N Engl J Med 376:429-439