Products

NEUPREX 

 

NEUPREX® (rBPI21, opebacan) is an injectable formulation of rBPI21, a modified recombinant fragment of BPI (bactericidal/permeability-increasing protein). BPI is a human host-defense protein made by PMN (polymorphonuclear) leukocytes—a type of white blood cell important in the body’s defenses against microbial infection.

 

BPI kills gram-negative bacteria, enhances the activity of antibiotics, neutralizes gram-negative endotoxin (a toxic molecule within the cell walls of gram-negative bacteria that can trigger local and systemic inflammatory reactions in the human host) and inhibits angiogenesis (blood vessel growth). Scientists at XOMA developed a 21Kd recombinant version of BPI referred to as rBPI21 or opebacan, which has the same activities as BPI. These characteristics underlie the rationale for testing opebacan in multiple infectious and inflammatory disease indications. More than 2000 patients have taken part in NEUPREX® clinical studies without any apparent safety concerns.

 

Congenital Heart Disease, Pediatric Open Heart Surgery (OHS) with Cardiopulmonary Bypass (CPB)

 

In October of 2003, XOMA and Children's Medical Center Dallas initiated an open-label, investigator-sponsored, single-center Phase I/II dose-escalation clinical study of NEUPREX® (opebacan) in pediatric patients with congenital heart abnormalities requiring OHS with CPB. The study is investigating dosing, efficacy endpoints and safety to assess the potential for conducting larger, additional studies.

 

In collaboration with investigators at the University of Texas Southwestern Medical Center, XOMA is currently conducting a study of the therapeutic effects of NEUPREX® (opebacan) treatment in patients with severe burn injury.

 

XOMA is working with the world’s leading experts at the Dana-Farber Cancer Institute and Childrens Hospital Boston/Harvard Medical School to investigate the potential therapeutic benefit of NEUPREX® (opebacan) in allogeneic hematopoeitic stem cell transplants (donor progenitor cell transplantation). This study will investigate dosing, efficacy endpoints and safety to assess the potential for conducting larger, additional studies.

 

XOMA has tested NEUPREX® in human clinical trials for several infectious and inflammatory conditions. Results of a Phase III study in severe pediatric meningococcemia (also known as meningococcal sepsis) patients were published in The Lancet in September 2000 (PDF).

 

NEUPREX® is an investigational drug currently under clinical development.

 

XOMA’s BPI-related patent portfolio includes more than 80 issued US patents, a number of US patent applications and corresponding foreign patents and applications directed to novel compounds and compositions, manufacturing methods, formulations, and therapeutic uses of BPI protein products. The portfolio includes a number of patents exclusively licensed from NYU School of Medicine and Incyte Corporation.

 

ANTI-GASTRIN Mab

 

In September of 2004, XOMA and Aphton Corporation announced a worldwide collaboration to develop treatments for gastrointestinal (GI) and other gastrin-sensitive cancers using anti-gastrin monoclonal antibodies.

 

Antibodies to be developed under the collaboration will bind and neutralize the hormone gastrin that is known to be involved in tumor progression in GI cancers. Gastrin expression and the appearance of gastrin receptors have been associated with increasing malignant characteristics of GI tumors and with poorer prognostic outcomes. Specifically, gastrin is known to be involved in the progression of colorectal, stomach, liver and pancreatic cancers and inhibiting gastrin may inhibit such growth.

Gastrin is a circulating peptide hormone responsible for stimulation of gastric acid secretion. In addition, it acts as a potent growth factor promoting the growth of normal gastric mucosa as well as a variety of GI cancers (gastric, pancreatic, colorectal). Gastrin secreted by normal gastric cells or tumor cells functions by binding to the gastrin/CCK-2 receptor initiating a number of downstream events. These events can be inhibited by an antibody neutralizing gastrin.

Gastrin is found in several different forms in the body which are all products of post-translational processing of the 101 amino acid gene product. The three most important species in terms of biologic activity and amount found in the serum are a 34 amino acid - G34; a 17 amino acid form - G17; and, the glycine extended G17 (Gly-G17) which is a precursor to G17 in which the c-terminal end has a glycine attached. Conventionally, gastrin is synomous with G17. In a homeostatic situation gastrin is produced by the G-cells of the antral mucosa of the stomach and its functions are to prepare the stomach for ingestion of food by stimulating the secretion of gastric acid (parietal cell-derived HCl) and pepsin. Gastrin also serves as a trophic factor by stimulating the growth of the mucosa of the digestive tract.

 

Gastrin’s functions as a trophic factor are of importance in cancer. Data from several laboratories have indicated that several tumor types produce and secrete gastrin and that gastrin serves as a growth factor for many cancer types. These cancer types include colorectal, pancreatic, gastric, thyroid, and lung cancer. The data has indicated that gastrin can act as growth factor through autocrine, paracrine as well as endocrine stimulation of tumor cells.

 

XOMA and Aphton are working together to develop therapeutic grade inhibitory Mabs to block the pathological functions of gastrin as a novel treatment for GI cancers. This program is currently in preclinical development.

 

Gastrin, CCK, Signaling, and Cancer (PDF) Annu. Rev. Physiol. 2001. 63:49-76.
Pancreatic cancer
Caplin et al, 2000; Goetze et al, 2000
Prasad et al, 2005
Colorectal cancer
Ciccotostso et al, 1995; Kochman et al, 1992
Nemeth et al, 1993; Schmitz et al, 2001
Monstein et al 2004; Mukawa et al, 2005
Gastric cancer
Henwood et al, 2001