Titan receives FDA approval to initiate Phase I clinical trial and pilot study for anticancer agents.

MENLO PARK, Calif.--(BUSINESS WIRE)--Feb. 1, 1995--Titan Pharmaceuticals Inc., today announced that Ansan Inc., one of Titan's operating companies, has received approval for its Investigational New Drug (IND) application from the Food and Drug Administration (FDA) to initiate a Phase I clinical trial for AN-9, a novel anticancer agent.

AN-9 is a butyric acid-based molecular agent which, in laboratory and preclinical tests, has demonstrated broad anticancer activity, while exhibiting much lower toxicity than traditional chemotherapeutic agents.

"A major challenge in the current use of chemotherapy is obtaining efficacy while avoiding the toxicities which limit treatment," said Louis R. Bucalo, M.D., president and chief executive officer of Titan.

"To address this problem, Ansan is developing a class of compounds which are based upon butyric acid, a non-toxic, naturally occurring molecule. In laboratory and preclinical tests, AN-9 has displayed relatively little toxicity, compared to traditional cancer drugs, and broad anticancer activity. We are encouraged to be taking this first step in clinical testing for AN-9."

Ansan's butyric acid derivatives employ a novel approach to cancer treatment called differentiation therapy, which causes rapidly growing, immature cells to become growth-regulated, differentiated cells. In addition, some types of cancer cells are induced by these derivatives to undergo apoptosis, a programmed chain of intracellular, biochemical and molecular changes leading to cancer cell death.

The Phase I study will assess the safety of AN-9 in patients with a variety of solid tumors. It will be conducted at the Cancer Therapy and Research Center in San Antonio, Texas.

Titan also announced that Ingenex Inc. another of its operating companies, and its collaborators at The University of Texas M.D. Anderson Cancer Center have received FDA approval to begin a pilot, physician-sponsored clinical study to test Ingenex's proprietary multidrug resistance (MDR) gene therapy in breast cancer patients. The FDA had previously given similar approval to begin testing this MDR gene therapy in patients with ovarian cancer.

Patients in the breast cancer study will receive stem cells obtained from their peripheral blood. These cells will be genetically modified with Ingenex's proprietary MDR-1 gene. The MDR-1 gene protects bone marrow and blood cells from the toxicity of chemotherapy by producing P-glycoprotein, a protein which pumps anticancer drugs out of cells before the drugs can cause damage. The goal is to insert the MDR-1 gene into blood stem cells to protect against the dose-limiting side effects that often prevent more extensive treatment with traditional chemotherapeutic drugs.

"We are pleased to extend our pilot studies of MDR-1 gene therapy with this breast cancer study," said Dr. Bucalo. "There are many types of cancer for which the outcome could potentially be improved with increased chemotherapy treatment and Ingenex's MDR-1 gene therapy, if successful, could permit the safe use of more extensive treatment."

The pilot study will assess the ability to genetically modify blood precursor cells with the MDR-1 gene, enrich for the genetically modified cells in patients, and protect patients' blood cells from the toxic side effects of paclitaxel, a cancer therapeutic marketed in the United States by Bristol-Myers Squibb (NYSE:BMY) under the trade name Taxol(R).

This study will involve 10 patients with advanced breast cancer and will be performed at the University of Texas M.D. Anderson Cancer Center, under the direction of Albert B. Deisseroth, M.D., Ph.D., chairman of the department of Hematology and John J. Kavanagh, M.D., chief of the section of Gynecologic Medical Oncology.

"Initiation of these studies illustrates Titan's strategy of pursuing synergistic therapeutic technologies," said Dr. Bucalo. "Through Ansan and Ingenex, Titan is developing complementary approaches for reducing the toxicity and increasing the effectiveness of cancer treatment."

Titan Pharmaceuticals, based in Menlo Park, Calif., is a biopharmaceutical holding company engaged in the development of proprietary therapeutic products for cancer, human transplantation and blood cell disorders.

In addition to Ansan and Ingenex, Titan's other operating companies are Geneic Sciences Inc. and Theracell Inc.

Editor's Note: Background information is available by calling 212/696-4455 ext. 329 and selecting document 130.

CONTACT: Titan Pharmaceuticals Inc., Menlo Park

Louis R. Bucalo, 415/617-2090

or

Noonan/Russo Communications Inc., New York

Rich Tammero, 212/696-4455, ext. 222