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Pipex Therapeutics Inc. merged with the shell company Sheffield Pharmaceuticals Inc., disclosing at the same time positive data from the pivotal Phase III trial with its lead candidate Coprexa for Wilson's disease.

Sheffield went bankrupt in 2003, but the court "allowed the shares to be discharged, [in order] to get back some value for creditors," said Steve Kanzer, co-founder, chairman and CEO of Ann Arbor, Mich.-based Pipex, founded in 2001.

"From our standpoint, it was an opportunity to pick up a publicly traded entity," he added, and 98 percent of the stock is now owned by Pipex.

Shares of Sheffield (OTC BB:SFPH), of which Pipex has become a wholly owned subsidiary, closed Wednesday at $1.73, up 55 cents, or 46.6 percent. Pipex will apply shortly to trade under a different ticker, Kanzer said.

In the merger, a newly formed, special purpose subsidiary of Sheffield merged with Pipex in a stock-for-stock transaction, with Sheffield issuing shares to Pipex stockholders based on an exchange ratio that gave Pipex owners 34 million new shares of Sheffield (which has assumed outstanding options and warrants to buy Pipex stock, and will convert them into options or warrants to buy Sheffield).

Michael Manion, majority shareholder of Sheffield, as well as the firm's sole director and former CEO, sold Pipex about 2.4 million shares of common stock, which Pipex plans to retire. The merged company will be based in Ann Arbor and will continue the business operations of Pipex.

That work includes ongoing development of oral Coprexa (tetrathiomolybdate), most recently tested in 48 patients with Wilson's disease, an autosomal recessive genetic disease caused by mutations of the ATP7B gene but easily mistaken for other conditions.

"They spend the majority of their lives misdiagnosed as psychotic or schizophrenic," Kanzer told BioWorld Today. Not until patients show up with Parkinson's-like syndromes do further tests lead to a correct diagnosis.

People afflicted with the rare illness can't properly clear excess free copper from the body by way of the liver into the bile and stool, so the mineral accumulates, sending elevated levels into the cerebral spinal fluid and brain.

In the pivotal trial, patients were treated first with either Syprine (trientine, Merck & Co. Inc.), a copper chelator approved as second-line therapy for the treatment of Wilson's disease, or Coprexa, and then Galzin (zinc acetate, Gate Pharmaceutical Co.) maintenance therapy for two years.

Those given Syprine showed a 26 percent incidence (6 of 23) of neurologic worsening, but those treated with Coprexa showed only a 4 percent incidence (1 of 25) of the key Wilson's symptom (p<0.05).

Coprexa works "not just by chelating copper but controlling it by binding it to albumin, whereby it's ultimately released in the stool," Kanzer said. "There really are no good alternative therapies."

In recent years, a number of other diseases have been shown to involve copper, Kanzer said. Among them is idiopathic pulmonary fibrosis, which afflicts 120,000 people in the U.S., with 48,000 new cases reported annually. The fibrotic process needs copper to worsen. Primary biliary cirrhosis also is the target of Coprexa therapy, in an FDA-funded, 50-patient Phase II trial.

Pipex is developing oral Trimesta (estriol) for the treatment of relapsed/remitting multiple sclerosis. The drug, which has completed a Phase II study in that indication, is an estrogenic molecule, approved and marketed in Europe and Asia for the treatment of postmenopausal hot flashes for more than 40 years.

"MS patients who become pregnant have high rates of remission in the third trimester," Kanzer said. "Unfortunately, four to six weeks after delivering, they also have very high rates of relapse of their disease." Estriol - produced only during pregnancy - apparently confers immune benefits on the mother as well as the fetus.

Other investigators completed a 22-month Phase IIa trial that showed "very significant" reductions in the number and size of MS lesions, Kanzer said, and a trial by Pipex will start soon.

Nearing the finish of a dose-ranging Phase II trial is one of a series of small-molecule/peptidomimetic inhibitors of the CD4 co-receptor of T cells. Pipex is testing the compound for prevention of graft-vs.-host disease.

Pipex is testing Correcta (clotrimazole), an enema formulation of a widely used topical antifungal, in Phase II trials for acute pouchitis, a subset of inflammatory bowel disease related to ulcerative colitis. Effirma (flupirtine), Pipex's oral drug for fibromyalgia syndrome, has completed a pilot clinical study. Approved in Europe since 1984 for pain, the compound has not been cleared in the U.S. for any indication.

Pipex also is working on Solovax, a T-cell vaccine for MS. T cells reactive to myelin antigens are collected from the peripheral blood of an MS patient, expanded, attenuated and injected back into the patient as a vaccine - a "pretty neat approach to MS," Kanzer said. A grant from the National Institutes of Health supported an 80-patient, Phase II trial with the approach, but results have yet to be published.

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