Industry-Sponsored Research Week

Yale signs collaboration agreement with X4 Pharmaceuticals for rare disease research


By David Schwartz
Published: August 8th, 2017

Yale University and X4 Pharmaceuticals, a clinical stage biotech company developing novel CXCR4 inhibitor drugs to to treat cancer and rare diseases, have entered a a multi-year sponsored research agreement to develop and study a genetic model of WHIM syndrome, a rare genetic immunodeficiency disease which currently has no approved treatments.

The multi-year research collaboration will investigate the fundamental mechanisms that result in chronic immune deficiency in a genetic preclinical model of WHIM syndrome. The research will be conducted with João Pedro Pereira, PhD, associate professor of immunobiology and a member of Yale’s Stem Cell Center and Yale Cancer Center’s Program in Cancer Immunology. Dr. Pereira’s lab studies of the mechanisms of hematopoiesis, the fundamental and complex process that generates many different cell types including all immune cells, and its role in conferring immunity.

WHIM syndrome is a primary genetic immunodeficiency disease caused by mutations in the CXCR4 receptor gene resulting susceptibility to certain infections. WHIM is an abbreviation for the characteristic symptoms of the syndrome: Warts, Hypogammaglobulinemia, Infections, and Myelokathexis. Several thousand patients worldwide suffer from WHIM syndrome. Because patients are highly susceptible to infections, the disease has significant morbidity beginning in early childhood and continuing throughout life. Current therapy is limited to treatment of acute infections with antibiotics or prevention through the use of intravenous immunoglobulin. There is no approved therapy for the treatment of WHIM syndrome.

The drug candidate X4P-001-RD, an oral, small molecule inhibitor of CXCR4, is being developed for use as a life-long treatment for patients with WHIM syndrome and other primary genetic immunodeficiencies. It is currently being studied in a Phase 2/3 trial in patients with WHIM syndrome.

Within the bone marrow, a normally functioning CXCR4 receptor controls the release of neutrophils and leukocytes into the blood stream, thereby ensuring normal immune surveillance functions throughout the body. In patients with WHIM syndrome, however, mutations to the CXCR4 receptor cause aberrant signaling, which leads to retention of neutrophils and leukocytes in the bone marrow and inadequate immune function. X4P-001-RD is designed to normalize the signaling for the mutant CXCR4 receptor to promote the release of neutrophils and leukocytes, thereby restoring healthy immunity.

“The incorrect positioning of immune cells in primary and secondary immune organs due to CXCR4 mutations has been well documented,” said Dr. Pereira. “This research will elucidate the fundamental mechanisms that lead to chronic impairment of the immune system, particularly of long-term immunity, as a result of aberrant immune cell positioning and trafficking. CXCR4 plays a fundamental role in immunity and we look forward to more deeply understanding its impact on the immune system.”

“It is gratifying to work with a leading immunobiologist like Dr. Pereira, who has developed cutting edge technologies to study immune cell trafficking and function on a single cell level,” said Sudha Parasuraman, MD, X4’s chief medical officer. “X4’s research program with Yale offers the exciting possibility to gain mechanistic insights into WHIM syndrome and the role that CXCR4 plays broadly in immunity, so that we can further demonstrate the potential of our drug candidate, X4P-001-RD, to address the unmet need of patients with WHIM syndrome.”

Source: Business Wire

Posted under: University-Industry Engagement Week

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