Adherex Technologies Inc.
TSX : AHX
AMEX : ADH

Adherex Technologies Inc.

November 16, 2005 08:43 ET

Adherex Announces Global Development Plans for Advancing Eniluracil Into Phase III by Mid 2007

RESEARCH TRIANGLE PARK, NORTH CAROLINA--(CCNMatthews - Nov. 16, 2005) - Adherex Technologies Inc. (TSX:AHX) (AMEX:ADH), a biopharmaceutical company with a broad portfolio of oncology products under development, today announced its global development plans for the chemoenhancer eniluracil, which the Company in-licensed from GlaxoSmithKline (GSK) in July 2005. The Company expects to have eniluracil into Phase III trials by mid 2007.

Eniluracil is a drug designed to inhibit the breakdown of 5-FU, one of the world's most commonly used chemotherapies. Although 5-FU is a mainstay of contemporary cancer therapy, it has some therapeutic drawbacks, including that it must be given intravenously, it can cause severe and dose-limiting side effects, and it has variable blood and tissue levels which impact its anti-tumor activity and safety profile. In combination with eniluracil, 5-FU can become orally active, have fewer side effects, and more uniform and prolonged blood levels, thereby improving its effectiveness.

GSK's clinical development program for the combination of eniluracil and 5-FU met with success in early development. However, three Phase III trials undertaken by GSK failed and development was stopped. Since then, Adherex has generated data which provide a new understanding of the mechanism of action of eniluracil - namely, that eniluracil not only inhibits the breakdown of 5-FU, it also temporarily blocks the activation of 5-FU into the metabolites that are responsible for its anti-tumor activity. As a result, the Company has identified three factors that are necessary to optimize the combination of eniluracil and 5-FU: 1) the absolute dose of eniluracil, 2) the ratio between the eniluracil and 5-FU dosages, and 3) the schedule of administration of the two drugs.

"I have been enthusiastic for a long time about the potential for eniluracil to make 5-FU a better drug," said Robert Diasio, MD, Professor of Medicine (Hematology/Oncology), Pharmacology & Toxicology, and Genetics at the University of Alabama School of Medicine in Birmingham, Alabama and one of the world's most noted experts on 5-FU. "Indeed, the failure of the GSK Phase III trials of eniluracil was a surprise and disappointment. However, since GSK discontinued development, data has been generated which indicates that the anabolism of 5-FU can be significantly affected by eniluracil. I believe that the dose, dose ratio, and schedule of administering eniluracil and 5-FU are critical to achieving the optimal therapeutic effectiveness of 5-FU."

Clinical Development Program

To return eniluracil to Phase III trials by mid 2007, Adherex will begin its clinical development program with preliminary studies to further refine: 1) the optimal dose of eniluracil, 2) the optimal dose ratio and schedule of eniluracil in combination with 5-FU, and 3) the clinical response rate to the proper combination of the two drugs. Adherex expects to initiate the first of these studies shortly, with data available in the first half of 2006. The second study, scheduled to begin in the U.S. in early 2006, will enroll approximately 20 patients, primarily with breast cancer, and should be completed in six to eight months. Adherex expects to evolve this study into a Phase II trial in breast cancer, which could conclude in the first half of 2007.

In addition to these studies, Adherex plans to begin a Phase I/II clinical trial in hepatocellular (liver) cancer in Asia in the second quarter of 2006. A Phase III trial in liver cancer, one of the most common causes of cancer death worldwide, could begin by mid 2007.

Based on the results of these studies, Adherex may conduct additional studies in other cancer types, such as gastric, ovarian or lung cancer, where 5-FU is also widely used.

"In my view, Eniluracil represents a relatively low risk, high reward opportunity for Adherex," said William P. Peters, MD, PhD, MBA, Chairman and CEO. "It has the potential to become both an important value-generator for our Company and an effective tool for cancer physicians - improving the therapies available to their patients."

ADH-1

The Company also provided an update on its development of ADH-1, indicating that another patient has experienced tumor regression using ADH-1 as a single agent which fulfills the initial designation of a partial response. This patient, enrolled in the Phase Ib/II trial of ADH-1 in Europe, is a 61-year-old woman with chemotherapy-resistant cancer of the fallopian tube. She was treated with weekly doses of ADH-1 at 300 mg/m2 with limited response, then upon dose escalation to 600 mg/m2, began to show regression of her tumor, which has been enhanced with repetitive dosing.

Altogether, Adherex has now seen evidence of anti-tumor activity in five patients in its Phase I experience:

- The first patient was a 62-year-old woman with N-cadherin positive squamous cell cancer of the esophagus with lung metastases. This patient received 11 doses of ADH-1 at 188 mg/m2, maintained an objective partial response for six months and did not experience tumor progression for nine months.

- The second patient was a 24-year-old woman with N-cadherin positive cancer of the adrenal gland that secreted abnormally high hormone levels. This patient experienced a reduction in blood flow to her tumor 90 minutes following 150 mg/m2 of ADH-1, a drop in the abnormally high hormone levels after one week, and showed evidence of necrosis (cell death) on MRI scans after six weeks. She subsequently received 31 additional doses of ADH-1 under a Health Canada Special Access Program and experienced a relative normalization in her hormone levels with stable disease for approximately nine months.

- The third patient was a 56-year-old man with an unknown primary cancer and lung metastases that showed decreases of 39% and 14% in tumor masses on radiologic scans six weeks following a single dose of ADH-1.

- The fourth patient was a 42-year-old man with rapidly progressing metastatic colon cancer who experienced seven months of stable disease while receiving ADH-1

- The fifth patient was the 61-year-old woman with chemotherapy-resistant cancer of the fallopian tube mentioned above.

In conjunction with the announcement of the global development plans for eniluracil, the Company will be posting later today a document discussing the market opportunity of eniluracil on its website at www.adherex.com.

Conference Call

As previously announced, the Company will hold a conference call on November 16, 2005 at 10 a.m. ET to discuss its third quarter 2005 financial results and discuss the details for its eniluracil development program. This call will be webcast live via the Internet at www.adherex.com. The event will also be archived and available for telephone replay through November 21, 2005 and webcast replay through November 16, 2006.


Live Participant Dial In (Toll Free, Canadian and US callers): 800-946-0783

Live Participant Dial In (International): 719-457-2658

Conference Passcode: 9409555

Replay Number (Toll Free): 888-203-1112

Replay Number (International): 719-457-0820

Replay Passcode: 9409555


About Adherex Technologies

Adherex Technologies Inc. is a biopharmaceutical company dedicated to the discovery and development of novel cancer therapeutics. We aim to be a leader in developing innovative treatments that address important unmet medical needs in cancer. We currently have multiple products in the clinical stage of development, including ADH-1 (Exherin™), eniluracil and sodium thiosulfate (STS). ADH-1, our lead biotechnology compound, selectively targets N-cadherin, a protein present on certain tumor cells and established blood vessels that feed solid tumors. Eniluracil, an oral dihydropyrimidine dehydrogenase (DPD) inhibitor, was previously under development by GlaxoSmithKline for oncology indications. STS, a drug from our specialty pharmaceuticals pipeline, protects against the disabling hearing loss that can often result from treatment with platinum-based chemotherapy drugs. With a diversified portfolio of unique preclinical and clinical-stage cancer compounds and a management team with expertise in identifying, developing and commercializing novel cancer therapeutics, Adherex is emerging as a pioneering oncology company. For more information, please visit our website at www.adherex.com.

This press release contains forward-looking statements that involve significant risks and uncertainties. The actual results, performance or achievements of the Company might differ materially from the results, performance or achievements of the Company expressed or implied by such forward-looking statements. Such forward-looking statements include, without limitation, those regarding the development plans of the Company and the expected timing and results of such development. We can provide no assurance that such development will proceed as currently anticipated or that the expected timing or results of such development will be realized. We are subject to various risks, including those inherent in the biopharmaceutical industry, the early stage of our product candidates, the uncertainties of drug development, clinical trials and regulatory review, our reliance on collaborative partners, our need for additional capital to fund our operations, and our history of losses. For a more detailed discussion of related risk factors, please refer to our public filings available at www.sedar.com and www.sec.gov.

Contact Information

  • Adherex Technologies Inc.
    Melissa Matson
    Director, Corporate Communications
    (919) 484-8484
    matsonm@adherex.com