Development of an Anti-P-selectin Antibody for the Treatment of Sickle Cell Disea

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 1R44HL093893-01A1
Agency Tracking Number: HL093893
Amount: $3,342,790.00
Phase: Phase I
Program: SBIR
Awards Year: 2009
Solicitation Year: 2009
Solicitation Topic Code: N/A
Solicitation Number: PHS2009-2
Small Business Information
SELEXYS PHARMACEUTICALS CORPORATION
SELEXYS PHARMACEUTICALS CORPORATION, 840 RESEARCH PKWY, STE 516, OKLAHOMA CITY, OK, 73104
DUNS: 145737131
HUBZone Owned: Y
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 SCOTT ROLLINS
 (203) 776-1790
Business Contact
 RICHARD ALVAREX
Phone: (405) 319-8195
Email: ralvarez@selexys.com
Research Institution
N/A
Abstract
DESCRIPTION (provided by applicant): 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.

* information listed above is at the time of submission.

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