National Editor

TolerRx Inc. is holding up its initial public offering until the company can analyze preclinical data from one of its products to determine what impact the results might have on development timelines.

Douglas Ringler, president and CEO of Cambridge, Mass.-based TolerRx, told BioWorld Today that he could not disclose which product is at issue, nor could he comment further because of SEC-imposed quiet-period restrictions.

But in a press release, Ringler said company officials "remain confident that we will be able to move forward with the IPO in a timely manner after the completion of this analysis."

The company filed for its IPO in August, and in October set the number of shares at 4.7 million and the price at $12 to $14, which at the upper limit would raise $65.8 million. (See BioWorld Today, Aug. 28, 2003.)

In its prospectus, TolerRx noted that its pipeline of five products includes three in preclinical development.

One is TRX2, a humanized monoclonal antibody that binds to the CD8 receptor found on a subset of T cells, being studied in a renal transplantation experiment in nonhuman primates as combination therapy with TRX1. TRX1, which also is a humanized monoclonal antibody, is partnered with South San Francisco-based Genentech Inc. TRX1 is aimed at the CD4 antigen on T cells and is designed to generate tolerogenic immune responses. It completed a Phase I trial in July in which it was found to be generally well tolerated. (See BioWorld Today, Jan. 6, 2003.)

TRX2 is believed to be potentially synergistic with TRX1 for induction of immunological tolerance in organ transplantation, given the role that T cells bearing the CD8 receptor have in the early rejection of transplants. TRX2 is designed to deplete those T cells at the time of transplant so they don't cause rejection before immunological tolerance can be established by TRX1.

Genentech has a right of first negotiation for TRX2 and any rights to anti-CD8 antibodies if TolerRx looks to partner the drug.

The second preclinical candidate is TolerMab TRX3, another monoclonal antibody. That one binds to the CD2 receptor found on T cells and other subsets of lymphocytes. It's being studied for autoimmune diseases.

CD2 has been in the news for other reasons this year, when Cambridge, Mass.-based Biogen Inc.'s psoriasis treatment, Amevive (alefacept), was approved in late January. Amevive is a fusion protein that is directed at the CD2 antigen. (See BioWorld Today, Feb. 3, 2003.)

The company's TolerMab technology makes an antibody become immunologically recognized as "self" while maintaining therapeutic activity for long-term benefit; the third preclinical candidate also grew out of that methodology.

That candidate is TolerMab TRX4, a monoclonal antibody that binds to a receptor found on all T cells called CD3, which is involved in normal T-cell signaling. TRX4 is designed to block the function of T-effector cells that attack the body and cause autoimmune disease. It's being developed for Type I diabetes, psoriasis and psoriatic arthritis.

TRX4 also is in an investigator-sponsored Phase II trial in 80 patients in Europe with new-onset Type I diabetes. All patients had completed treatment and are in an 18-month follow-up phase, the company said in August. An investigational new drug application was expected for TRX4 for psoriasis and psoriatic arthritis by early 2004, and, later, for additional studies in new-onset Type I diabetes, based on results of the ongoing European trial.