SOURCE: Pipex Pharmaceuticals, Inc.

October 01, 2007 08:33 ET

Pipex Pharmaceuticals Files Pre-Investigational Device Exemption With FDA

FreeBound Submission Builds Upon Franchise for Treating Metal-Implicated Diseases

ANN ARBOR, MI--(Marketwire - October 1, 2007) - Pipex Pharmaceuticals, Inc. (AMEX: PP), a specialty pharmaceutical company developing innovative late-stage drug candidates for the treatment of neurologic and fibrotic diseases, announced today that it has submitted a pre-IDE (Investigational Device Exemption) application with the FDA for FreeBound™, Pipex's novel device for the rapid detection of free copper levels in blood serum.

"The submission of our pre-IDE application for the FreeBound device is another step in Pipex's strategy of building a leadership position in the field of diseases involving metal dyshomeostasis. FreeBound is intended to overcome the technical limitations of existing diagnostic technologies that are unable to directly measure levels of free metals in serum. The accurate and rapid measurement of free metals in serum may open up the possibility of diagnosing and managing diseases in which free serum metal dyshomeostasis is suspected, such as, Wilson's disease, Alzheimer's disease, Parkinson's disease, schizophrenia and autism," said Steve H. Kanzer, Chairman and Chief Executive Officer.

"We believe that making the FreeBound™ device commercially available may have the potential to identify patients having clinically relevant elevated levels of free serum copper and answer important questions regarding the potential role of metal dyshomeostasis in many diseases in which metal dyshomeostasis is suspected. Patients may then be suitable for treatment with a therapeutic agent capable of managing serum free metal levels, possibly opening up new approaches in the treatment and management of many important diseases. COPREXA™, our proprietary drug candidate, is a copper modifying agent, which has completed two Phase III clinical trials for the neurologic Wilson's disease, and for which we plan to submit an NDA filing to the FDA in November 2007."

"As a co-inventor and co-developer of the FreeBound™ device, we are excited about transitioning this novel technology from a concept toward clinical development in the management of serum based metals," said John S. Althaus, Vice President of Advanced Technologies of Pipex.

The pre-IDE application process is designed to provide companies that have unique diagnostic tests with informal input regarding what the FDA would look for in a formal IDE application. A submission made under the pre-IDE process is not an official IDE application as described in 21 CFR Part 812. The Pre-IDE process is designed to help companies obtain early, informal input on aspects of a future IDE application and offers assistance in establishing the parameters for official IDE applications when unique diagnostic tests involving innovative technologies are being pursued.

Currently, there is no convenient or FDA-approved diagnostic test to monitor levels of free copper levels in human serum.

The FreeBound™ Device

Copper, an essential metal, is made available to organs throughout the body via a tightly regulated system of copper chaperones and copper transport proteins within the body's systemic circulation. Normally, approximately 90 percent or more of serum copper is tightly bound to the serum copper chaperone called ceruloplasmin (Cp). The remaining 10 percent of serum copper represents the so-called "free" or "non-ceruloplasmin bound" copper pool, which may be highly toxic to the brain, the organ that is most sensitive to the effects of free copper. In Wilson's disease patients, the free copper pool is expanded and causes psychiatric symptoms and neurodegeneration in affected patients.

Direct and accurate measurement of this important toxic pool of free copper in serum has until now remained elusive. The current standard methodology for measuring free copper relies instead on an inexact, indirect estimate involving a two-step process. First, total serum copper is typically measured using an expensive and time-consuming technique called atomic absorption. Second, serum Cp concentrations are determined by immunoassay or enzymatic assay. Once the Cp measurement has been determined, the estimated amount of copper atoms believed to be bound to Cp is calculated and subtracted from total copper to arrive at an estimate of free copper in serum. The indirect result carries a large potential for error based on erroneous assumptions and experimental deviations from multiple measurements.

Pipex believes that, using the FreeBound™ device, free copper levels in blood serum may be determined using technology similar to and as simple to use as a glucometer, which incorporates electrochemical detection. With a glucometer, blood serum is applied to test strips attached to a meter. The FreeBound™ device is programmed to separate and measure free copper versus Cp-bound copper on the test strip, immediately displaying the results on the meter.

Wilson's disease serum samples were tested for free copper using the standard indirect method and compared to results directly measured using the FreeBound™ device. The advantage of the FreeBound™ device method is that it is direct, inexpensive, rapid (results displayed within minutes), user-friendly and may yield a more accurate measure of true free copper levels. The FreeBound™ device and test methods are the subject of pending patents owned by Pipex.

About COPREXA™

COPREXA™ is an oral, small-molecule, anti-copper agent that is highly specific for lowering the level of free copper in serum, the most toxic form of copper in the body. Thus, it may be suited for the treatment of central nervous system (CNS) diseases in which abnormal serum and CNS copper homeostasis are implicated. COPREXA™ has completed two pivotal clinical trials in 48 and 55 initially-presenting neurologic Wilson's disease patients, the results of which have been previously published(1)(2). Pipex is also developing COPREXA™ for fibrotic disorders based upon the rationale that the fibrotic disease process is dependent upon the availability of free copper in the body. COPREXA™ has demonstrated the ability to inhibit fibrosis in a number of well-established animal models through the sequestration of available copper and inhibition of key fibrotric cytokines, including secreted protein acid rich in cysteine (SPARC), NFkappaB, TGF-beta, FGF-2, IL-1, IL-6, IL-8, and connective tissue growth factor (CTGF).

COPREXA™ has completed a 20-patient, one-year, open label Phase I/II clinical trial for the treatment of refractory idiopathic pulmonary fibrosis (IPF), a fatal respiratory disease. The results of this trial were presented in May of this year at the annual meeting of the American Thoracic Society (ATS). Pipex is planning to initiate a Phase III clinical trial of COPREXA™ in IPF and, if successful, Pipex may be permitted to file a supplemental NDA for COPREXA™ for this additional indication. COPREXA™ is also in a phase II clinical trial for the treatment of primary biliary cirrhosis (PBC), a fibrotic disease of the liver.

(1) Brewer, G.J., et al., Treatment of Wilson's disease with ammonium tetrathiomolybdate: III. Initial therapy in a total of 55 neurologically affected patients and follow-up with zinc therapy. Arch Neurol. 2003 Mar; 60(3):379-85.

(2) Brewer, G.J., Askari, F., Lorincz, M.T., Carlson, M., Schilsky, M., Kluin, K.J., Hedera, P., Moretti, P., Fink, J.K., Tankanow, R., et al. 2006. Treatment of Wilson's disease with ammonium tetrathiomolybdate: IV. Comparison of tetrathiomolybdate and trientine in a double-blind study of treatment of the neurologic presentation of Wilson's disease. Arch Neurol 63:521-527.

About Wilson's Disease

Wilson's disease is an autosomal recessive genetic disease attributable to mutations of the ATP7B gene. Worldwide, it is estimated that there are about 50 million heterozygous carriers of the mutated gene. These mutations lead to an inability to properly clear excess free copper from the body via the liver into the bile and stool. As a result, copper accumulates in the liver and elevated levels of toxic free copper enter the systemic circulation, cross the blood brain barrier, and enter the cerebral spinal fluid (CSF) and brain. These increased levels of free copper cause significant neurologic damage, resulting in tremors, impaired speech, and Parkinson's-like dystonia.

Psychiatric symptoms of neurologically-presenting Wilson's disease patients will generally precede neurologic symptoms by months or years and may include loss of emotional control, temper tantrums, emotional outbursts, bouts of crying, severe depression, suicidal ideation, loss of inhibitions, delusions, hallucinations and loss of ability to focus on tasks. Neurologic symptoms later develop as a result of neurodegeneration in the basal ganglia of the brain and include impaired speech, tremor, dystonia, incoordination and dysphasia. Crippling movement disorders may ultimately occur. Without proper treatment, Wilson's disease is usually fatal by the age of 30. However, if treatment is begun early enough, symptomatic recovery is usually complete and a life of normal length and quality can be expected.

About Pipex Pharmaceuticals, Inc.

Pipex Pharmaceuticals, Inc. ("Pipex") is a specialty pharmaceutical company that is developing proprietary, late-stage drug candidates for the treatment of neurologic and fibrotic diseases. Pipex's strategy is to exclusively in-license proprietary, clinical-stage drug candidates and complete the further clinical testing, manufacturing and regulatory requirements sufficient to seek marketing authorizations via the filing of New Drug Applications (NDAs) with the FDA in the US and Marketing Application Authorizations (MAAs) with the European Medicines Evaluation Agency (EMEA). For further information please visit www.pipexinc.com.

This press release contains forward-looking statements, within the meaning of Section 21E of the Securities Exchange Act of 1934, that reflect Pipex Pharmaceuticals, Inc.'s current expectations about its future results, performance, prospects and opportunities, including statements regarding the IDE filing for COPREXA™ with the FDA, as well as our proposed marketing of FreeBound™. Where possible, the Company has tried to identify these forward-looking statements by using words such as "anticipates," "believes," "intends," or similar expressions. These statements are subject to a number of risks, uncertainties and other factors that could cause actual events or results in future periods to differ materially from what is expressed in, or implied by, these statements including the risks set forth in our Form 10-KSB and other filings with the Securities and Exchange Commission. We cannot assure you that we will be able to successfully develop or commercialize products based on our technologies, including COPREXA™, TRIMESTA™, zinc-monocysteine, EFFIRMA™, SOLOVAX™, or Anti-CD4 802-2, particularly in light of the significant uncertainty inherent in developing, manufacturing and conducting preclinical and clinical trials of new pharmaceuticals, and obtaining regulatory approvals, that our technologies will prove to be safe and effective, that our cash expenditures will not exceed projected levels, that we will be able to obtain future financing or funds when needed, that product development and commercialization efforts will not be reduced or discontinued due to difficulties or delays in clinical trials or due to lack of progress or positive results from research and development efforts, that we will be able to successfully obtain any further grants and awards, maintain our existing grants which are subject to performance, that we will be able to patent, register or protect our technology from challenge and products from competition or maintain or expand our license agreements with our current licensors, or that our business strategy will be successful. All forward-looking statements made in this press release are made as of the date hereof, and the Company assumes no obligation to update the forward-looking statements included in this news release whether as a result of new information, future events, or otherwise.

Contact Information

  • For Further Information Contact:

    Steve H. Kanzer, CPA, Esq.
    Chairman and Chief Executive Officer
    (734) 332-7800

    Thomas Redington (Investor Relations)
    Redington, Inc.
    (203) 222-7399