Assistant Managing Editor

Specialty pharma firm Pipex Pharmaceuticals Inc. expanded its autoimmune disease portfolio with the addition of an oral heat-shock protein-derived peptide that recently yielded promising results in a 160-patient Phase III trial in rheumatoid arthritis (RA), along with a compelling safety profile that could set it apart from other drugs in the crowded RA market.

Under the terms, Ann Arbor, Mich.-based Pipex gained rights to the drug, dnaJP1, a computer-designed drug discovered by Salvatore Albani, chairman of the Arizona Arthritis Center at the University of Arizona. Specific financial details were not disclosed.

Heat-shock proteins and dnaJ are up-regulated during cellular stress, which is triggered by inflammation and autoimmune diseases, so dnaJP1 aims to work by causing T-cell function to shift from inflammatory to regulatory, which, in turn, inhibits disease-related inflammation and induces a tolerogenic immunologic response. Data from the recent RA Phase II study, funded in part by a $5 million grant from the National Institutes of Health, showed that the proportion of dnaJP1-treated patients who achieved an ACR20 response at days 112, 140, 168 and follow-up was significantly higher than that of placebo-treated subjects.

ACR20 refers to a composite endpoint developed by the American College of Rheumatology and is used as scoring criteria for measuring RA treatment.

Data also showed that dnaJP1 demonstrated an 80 percent reduction in the production in vitro of tumor necrosis factor (TNF)-alpha by T cells. TNF-alpha is a well-known cytokine associated with RA and is the target of existing blockbuster drugs, such as Thousand Oaks, Calif.-based Amgen Inc.'s Enbrel (etanercept), which pulled in sales of $841 million in the second quarter. Enbrel is marketed for RA, psoriasis, psoriatic arthritis, ankylosing spondylitis and juvenile RA.

Centocor Inc., of Horsham, Pa., and Abbott, of Abbot Park, Ill., also market TNF-alpha inhibitors Remicade (infliximab) and Humira (adalimumab), respectively. All three of those drugs, however, are administered via injection, as are two other near-term candidates - Cimzia, a PEGylated TNF-alpha inhibitor from UCB SA, of Brussels, Belgium, and Centocor's next-generation TNF-alpha antibody drug golimumab, both of which are under FDA review - so an oral treatment option could represent a much-need option in the RA landscape.

And Pipex is not alone in that quest - other firms are working on oral TNF-alpha inhibitors, such as Mechelen, Belgium-based Galapagos NV, which signed an impressive preclinical RA deal with a Johnson & Johnson unit late last year - though Pipex is hoping its oral dnaJP1 will have other characteristics that lend it advantages over existing treatments. For instance, the company reported that studies to date have indicated that dnaJP1 might avoid some of the toxicities seen with the injectable therapies - Enbrel, Remicade and Humira all have black-box warnings relating to infection risks.

DnaJp1 also has been shown to work via a mechanism that might make it complementary to current biologics. In a preclinical study, an animal equivalent of dnaJP1, in combination with low-dose Enbrel, demonstrated significant reduction of mean arthritis scores on day 23 vs. placebo. Combination therapy also led to significant improvement of the histological score in the joints and produced an antigen-specific increase of tolerogenic cytokines, including production of IL-10 and IL-4 and up-regulation of CTLA-4 expression.

Pipex executives could not be reached for comment, but CEO Nicholas Stergis said in a press release that the firm was "equally impressed with the rigor and quality of the scientific data" surrounding dnaJP1, and added that Pipex anticipates reporting additional clinical results later this year.

The company, which focuses its efforts in the areas of central nervous system and autoimmune diseases, said the addition of dnaJP1 complements its advancing pipeline in immunology, which includes Trimesta, an oral, once-daily formulation of the hormone estriol that is in Phase II/III testing in relapsing-remitting multiple sclerosis.

Other Pipex programs include oral Zinthionein, which recently demonstrated statistically significant improvement in visual acuity at six months in a Phase II trial in dry age-related macular degeneration, and oral flupirtine, which is set to start Phase II testing in 90 fibromyalgia patients. Earlier in development, the company is working on small-molecule inhibitors of the CD4 co-receptor, which is related to autoimmune diseases such as MS.

In January, Pipex suffered a setback with its lead program, Coprexa (tetrathiomolybdate), when the FDA rejected its new drug application in initially presenting neurologic Wilson's disease. Two months later, the firm cut 14 staff positions to help reduce operating expenses. (See BioWorld Today, Jan. 30, 2008.)

The company, which recorded a net loss of $1.8 million, or 9 cents per share, for the second quarter, had about $7.5 million in cash as of June 30. At the time of its earnings report, the firm said its existing working capital would carry the firm for 15 months.

Shares of Pipex (AMEX:PP) closed at 70 cents Tuesday, down 1 cent.