Titan Pharmaceuticals Inc. is not your ordinary biotechnologystart-up.
First of all, it's actually a holding company, with fourindependently operated biotechnology businesses whosetechnologies are complementary. Secondly, it's about to receive$17.5 million in first-round financing from an oversubscribedoffering to venture capitalists and institutional investors.
This offering, led by Paramount Capital and scheduled to closeTuesday, follows by 18 months Titan's founding -- with thehelp of $1.2 million in seed capital from The Castle Group Ltd.
"Titan was formed to combine the efforts of synergistic andcomplementary groups," explained Louis Bucalo, the company'schief executive officer. Bucalo, who had been the associatedirector of clinical research at Genentech Inc. (NYSE:GNE),explained that Titan's overall strategy is to developtherapeutics in the areas of transplantation, blood celldisorders and cancer therapy through the four operatingcompanies in which Titan holds a majority interest: GeneicSciences Inc., Theracell Inc., Ingenex Inc. and Ansan Inc. Eachhas its own scientific advisory board.
Geneic Sciences Inc.
Founded with Suzanne Ildstad of the University of PittsburghSchool of Medicine, Geneic Sciences is developing technology forenabling permanent allogeneic (unmatched) tissue transplants.
The problem with current transplantations is that recipients ofantigenically distinct tissues from unmatched donors oftendevelop graft vs. host disease, a potentially fatal complication.For these patients to retain the graft at all, they have to bemaintained on immunosuppressive drugs. Even then, Bucalosaid, it's been found that more than 80 percent of allogeneickidney transplants fail within 10 years, 20 percent within thefirst year after surgery.
Geneic Sciences' core technology involves the use of a subset ofbone marrow progenitor cells known as facilitating cells, whichrepresent naturally less than 1 percent of the mammalian bonemarrow, Bucalo said.
"Many research groups, including ourselves, havedemonstrated that the stem cell by itself doesn't readilyengraft in an unmatched environment," he explained. But thefacilitating cells allow those precursors to do so.
In fact, in animal models these transplants have been achievedwithin and between species, without the need for matchingdonor and recipient and without the use of chronicimmunosuppressive drugs, Bucalo said.
Titan's operating company, Theracell Inc., on the other hand, isfocused on developing cell therapies for various neuraldeficiency diseases and neurological disorders. Theracell's coretechnology, developed by Bruce Cherksey at New YorkUniversity's medical center, enables cells of neural andparaneural origin to be transplanted into the brain by attachingthem to microcarriers. Thus, cells secreting particularneurotransmitters or growth factors could be implanteddirectly into the brain via microinjection, where they couldthen potentially correct biochemical deficiencies andimbalances.
The researchers have already used the technology to reverseanimal models of Parkinson's disease by injecting microcarriersloaded with normal human cells that elaborate dopamine,Bucalo told BioWorld. They've seen no evidence of rejection orinflammation, and the microinjected cells have a long-termviability of 90 percent, he added.
The third arm of Titan Pharmaceuticals is Ingenex, which wasfounded with Igor Roninson from the University of Illinois,Chicago, to develop therapies for treating drug-resistantcancers. The company is the exclusive licensee of two issuedU.S. patents -- one held by Roninson's institution, the other byMassachusetts Institute of Technology -- on multiple drugresistance (MDR), explained Bucalo.
The patents cover "both the human gene for MDR and the useof MDR genes to confer resistance to chemotherapy agents," hesaid. Thus, the company is developing methods for inducingmultidrug resistance to chemotherapies in normal cells such asbone marrow. It's also working on the inverse situation bydesigning ways to overcome multidrug resistance in cancercells, making them more susceptible to chemotherapy.
Ansan Inc. adds to the Titan technology mix its methods fordeveloping synthetic analogs of the natural molecule butyricacid for use in chemotherapy and blood cell disorders. "Butyricacid is a differentiation agent; its use can cause cancer cells tomature so they become 'normal' and go through a natural celldeath," Bucalo told BioWorld. But the problem with butyric acidper se is that the body clears it too quickly.
Scientists at Ansan, which was founded with researchers atIsrael's Bar-Ilan University, are developing analogs that have ademonstrated potency in vivo with minimal toxicity. "Theanalogs act as prodrugs to provide high levels of butyric acidintracellularly," Bucalo said.
The overriding factor in all of Titan's businesses is that thetechnologies should not only provide a medical benefit, butshould "provide a basis for the reduction in the cost of healthcare," according to Bucalo. "Titan Pharmaceuticals is not adiversification strategy, it's a company with a commonobjective," Bucalo told BioWorld.
-- Jennifer Van Brunt Senior Editor
(c) 1997 American Health Consultants. All rights reserved.