A second company operating under the Titan Pharmaceuticals Inc.umbrella has filed for an initial public offering.

Ingenex Inc., of Menlo Park, Calif., proposed Tuesday the sale of1.85 million shares of stock at $8.50 to $9.50 per share. At $9 theoffering would gross nearly $16.7 million. Kaufman Bros. LLC, ofNew York, is underwriting the offering and can purchase anadditional 277,500 shares to cover overallotments.

Titan can buy 222,222 shares in the offering and, assuming thatpurchase, would own about 54 percent of Ingenex (51 percent if theoverallotment option is exercised).

Ingenex is developing gene-based therapies and applying functionalgenetics to drug discovery, with an initial strategy to develop genetherapies for oncology indications.

Ingenex is sponsoring a Phase I/II trial based on the insertion andexpression of MDR-1, the human multidrug resistance gene, intoblood progenitor of stem cells purified from bone marrow or blood.Introduction of the gene is designed to make the cells less sensitive tocytotoxic drugs, allowing for more aggressive chemotherapy.

The trial of the product, MDRx1, involves 20 patients with breast orovarian cancer who then underwent bone marrow transplantation withtheir own modified cells. The trial, at The University of Texas M.D.Anderson Cancer Center, is designed to assess whether thegenetically modified cells can safely be reintroduced and maintainedin patients as they undergo multiple cycles of chemotherapy atincreasing doses.

Another program at Ingenex centers around the tumor suppressorgene, RB. Collaborators at M.D. Anderson reported that RB94produces a shorter, more stable protein than the naturally occurringfull-length gene. Preclinical studies showed the addition of RB94 toRB-deficient cancer cells prevented tumor growth more completelythan the addition of the full gene. Also, the company said RB94 mayhave broader utility since it blocks the growth of certain tumors stillcontaining the full RB gene. An investigational new drug applicationto test RB94 against prostate cancer is expected to be filed late in1997.

Ingenex's GSX System is used to identify genes based on theirfunctional roles in a biological or disease process. The system selectsshort gene fragments that inhibit a certain process and confer amedically desirable cellular property. The company is collaboratingon the system with researchers at the University of Illinois atChicago.

The system is being used both to gain insight into specific functionsof known genes and to discover new genes and fragments. Ingenexhas used the system to identify a gene fragment capable of blockingHIV replication, and is using it to discover drugs for diseasescharacterized by aberrant cellular function.

After the offering Ingenex will have about 4.8 million sharesoutstanding. That doesn't include about 1.3 million shares that couldbe issued upon the exercise of outstanding warrants and options.Titan had about $9.2 million in cash on March 31, 1996.

Titan, of South San Francisco, also holds majority positions in thefollowing private companies: Ascalon Inc., a Scottsdale, Ariz.,company developing therapeutic cancer vaccines; ProNeura Inc., ofSouth San Francisco, which is developing an implantable deliverysystem for central nervous system (CNS) indications; and TheracellInc., of Sommerville, N.J., which is developing drugs for CNSdisorders. Titan owns about 45 percent of South San Francisco-basedAnsan Inc., which went public in August 1995. n

-- Jim Shrine

(c) 1997 American Health Consultants. All rights reserved.