Tolerx, Inc (CAMBRIDGE, Massachusetts), a biopharmaceutical company engaged in the discovery and development of novel therapies for the treatment of immune-mediated diseases, announced the successful completion of a phase Ib clinical study of TRX1, a humanized anti-CD4 monoclonal antibody, in subjects with refractory cutaneous lupus erythematosus. The multicenter, multiple-dose, open-label, dose-escalation study was designed to assess the safety, tolerability, and pharmacokinetics of TRX1. Tolerx has received a milestone payment from Genentech, Inc in conjunction with the study's completion.

In a single-dose, placebo-controlled, double-blind, phase Ia trial that assessed the safety and pharmacokinetic parameters of TRX1, the compound appeared to be well tolerated and did not deplete T-cells; first-dose side effects such as fevers, chills, and hypotension was not observed.

TRX1 binds to the CD4 receptor found on both T-effector cells and T-regulatory cells. TRX1 is anticipated to block activation and function of T-effector cells and to favor dominance of T-regulatory cells, resulting in hyporesponsiveness, or tolerance, to antigens. In nonhuman primates, a short course of TRX1 can induce a long-term, antigen-specific tolerance to a normally immunogenic protein without compromising normal immune function. This suppression may have therapeutic benefit in treating autoimmune diseases that occur when the human immune system mistakenly identifies components of the human body as foreign. In collaboration with Genentech, preclinical data suggest that TRX1 may be effective in lupus and multiple sclerosis models.

Tolerx and Genentech collaborated in 2002 to develop and commercialize certain anti-CD4 monoclonal antibodies, including TRX1. Pursuant to the arrangement, Genentech may undertake further development, manufacturing, and commercialization of those anti-CD4 molecules in any indication. The agreement provides for Tolerx to potentially receive development and regulatory milestone payments, in addition to royalties on worldwide net sales of those anti-CD4 antibodies. Tolerx can also participate in a loss and profit sharing arrangement with Genentech in the US.