FOR IMMEDIATE RELEASE

Contact: Clarice Merrill,
Director Finance and Administration
Direct Therapeutics, Inc.
(650) 306-1270, ext. 2

Direct Therapeutics Announces Two Phase I/II Clinical Trials Of DTI-015 In Brain Tumors

(Redwood City, CA, October 3, 2000) - Direct Therapeutics Inc., (DTI), a privately held drug development company, today announced that enrollment has opened for two Phase I/II clinical trials using its DTI-015 drug candidate for the direct treatment of glioblastoma multiforme (GBM), the most common primary form of brain cancer.

DTI-015 is a unique product that contains the chemotherapeutic drug carmustine, also known as BCNU, dissolved in absolute ethanol. Solvent facilitated perfusion of BCNU enables the drug to enter both the aqueous and lipid compartments of target tissue, thus achieving rapid drug saturation of the tumor and selective elimination of cancer cells. DTI-015 is administered by image-guided stereotactic injection directly into the tumor, maximizing therapeutic effect while minimizing systemic toxicity and surgical intervention.

One of the trials is a multicenter, open-label Phase I/II study in patients who have a first GBM recurrence that cannot be removed surgically. This dose escalation study will assess the safety and activity of DTI-015 in up to 30 patients. The second trial is a single-center study that will assess the safety and pharmacokinetics of DTI-015 administered just prior to surgical removal of GBM or metastatic tumors of the brain.

"These clinical trials follow Food and Drug Administration (FDA) acceptance of our Investigational New Drug (IND) application for DTI-015," said Edward E. Luck, president and chief executive officer. "DTI has already been evaluated under physician-sponsored INDs in 50 patients with recurrent brain tumors or liver cancer. Encouraging preliminary results from those trials supported our IND filing and clinical development plan."

To date, more than 30 patients with inoperable brain tumors have been treated with DTI-015 at the University of Texas M.D. Anderson Cancer Center (Houston, TX). A preliminary analysis indicates that DTI-015 treatment was well-tolerated within the context of the disease, and resulted in median survival of 45 weeks among GBM patients. This compares with a well-established survival rate of 20 to 26 weeks among recurrent GBM patients.

"A major challenge to improving local GBM therapy is to effectively treat beyond the tumor margins into the surrounding brain tissue which harbor infiltrating tumor cells," said Victor A. Levin, M.D., professor of neuro-oncology at M.D. Anderson. Dr. Levin is also chairman of DTI's Scientific Advisory Board and a principal investigator for the Phase I/II study. "We hope to better understand how best to deliver DTI-015 to an beyond the surgical margins."

Samuel Hassenbusch, M.D., Ph.D., associate professor of neurosurgery at M.D. Anderson and a principal investigator for the Phase I/II study, said, "Further, in patients whose tumors are partially respectable, DTI-015 may effectively treat the inoperable portion of disease and improve outcome. For those patients whose tumors are inoperable because they are in eloquent brain areas, DTI-015 may offer the ability to quickly and decisively control the growth of these tumors."

In addition to M.D. Anderson, centers participating in the multicenter trial include the University of California, San Francisco (UCSF), Evanston Hospital (Evanston, IL), Lee Moffett Cancer Center (Tampa, FL), Mayfield Clinic (Cincinnati, OH), Stanford Medical Center (Stanford, CA) and University of Southern California (Los Angeles, CA). The single-center pharmacokinetic study is being conducted at UCSF.

Each year in the U.S., there are nearly 18,000 new diagnoses and 13,000 deaths due to brain tumors, according to the American Cancer Society. With currently approved therapy, most patients die within one year of first diagnosis or within six months of recurrence.

As recently announced by DTI, the FDA has granted Orphan Drug designation for the use of DTI-015 in the treatment of primary GBM. Orphan Drug status provides a seven-year period of post-approval marketing exclusivity for drugs that offer significant therapeutic advantage over approved treatments of conditions that affect 200,000 or fewer patients per year in the U.S.

DTI is also applying its technology platform for the treatment of tumors of the liver, one of the most common sites for tumor metastasis. Other cancers that may be treatable using DTI's technology include melanoma, lung, breast and prostate cancer.

Direct Therapeutics, Inc. is a drug development company using its proprietary solvent facilitated perfusion technology to address the delivery and distribution of drugs for the localized and regional treatment of cancer. Its technology encompasses the development of new products containing anticancer drugs and certain organic solvents that facilitate the penetration of drug throughout tumor tissue and into tumor cells.