By Jim Shrine

Special To BioWorld Today

Inex Pharmaceuticals Corp. and partner Schwarz Pharma AG stopped development of a restenosis drug candidate that failed to show benefit in a pilot Phase II trial.

The antisense drug, a synthetic oligonucleotide called INX-3280, was being developed for cardiovascular restenosis in North America and Europe by Schwarz, of Monheim, Germany. Inex, of Vancouver, British Columbia, bought INX-3280 and two anticancer candidates — along with intellectual property and manufacturing facilities — from Lynx Therapeutics Inc., of Hayward, Calif., in February for about US$7.5 million in cash and stock. (See BioWorld Today, Feb. 6, 1998, p. 1.)

Inex and Schwarz reported in August that a 10 mg dose of INX-3280 failed to decrease restenosis. The drug was designed to block the function of the c-myc gene, which is associated with restenosis.

David Main, Inex's vice president of corporate development, said the failure of INX-3280 has no financial impact on Inex, since development was being funded by Schwarz, and since Inex's resources are focused on cancer programs. Inex's Transmembrane Carrier Systems (TCS) delivery technology was not being used in the restenosis study.

Last month, Inex said it would trim expenses from C$1 million (US$651,040) to C$700,000 per month and focus on three preclinical drug candidates. The company said it expected to have about C$12.8 million in cash at the end of the third quarter, with 11 million shares outstanding.

Main said the September restructuring entailed deferring work on earlier-stage programs, stopping several collaborations with academic institutions, and trimming staff by 25 percent, to 66 employees. Collaborations with other biotechnology companies already had been discontinued.

"We wanted to have greater flexibility from the financial markets," Main said. "They are closed to companies such as ourselves right now. And we wanted to move some of these products into the clinic as soon as possible and not be so spread out."

The Phase II trial of INX-3280 involved combining the drug with a local delivery catheter. It did show that direct delivery into the coronary artery was safe and nontoxic. Those results were presented at the 20th Annual Congress of the European Society of Cardiology, in Vienna, Austria.

INX-3280 still is being developed in Japan by Tanabe Seiyaku Co. Ltd., of Osaka. The companies are discussing the implications of the preclinical and clinical results. The collaborations for Tanabe and Schwarz were both originally with Lynx.

Inex's TCS technology, which transports antisense drugs and gene plasmids to the interior of cells, is used in each of the three drug candidates still being developed. TCS is a combination of lipids, polymers and "fusogenic" factors that protects nucleic acids in the bloodstream from being cleared or degraded, and fuses to the cell, resulting in intracellular uptake of the compounds.

Main said the technology could be important overcoming some of the barriers facing delivery of antisense drugs or genes.

One of Inex's drug candidates is INXC-6295, an antisense drug encapsulated in TCS that targets the c-myc gene, which has been implicated in the growth of a variety of tumors. Inex expects to file an investigational new drug (IND) application within three or four months.

INX-4437 is designed to shrink tumors by blocking the receptor to insulin-like growth factor type 1. The company said that drug is expected to be ready for the clinic by the middle or end of next year.

Unlike the antisense drugs, the third candidate, INXC-gTK, is a gene plasmid. It combines the thymidine kinase (TK) gene and the drug ganciclovir. Inex's theory is that, after delivery to the interior of cancer cells, the TK gene synthesizes a protein that converts ganciclovir into a toxic form that kills the cells. The strategy with that drug is to move into clinical trials once additional financing or a partner is in place. Pre-IND requirements are expected to be completed in six months.

Data from a Phase II lymphoma trial of another Inex product, Onco TCS, are expected by the end of the month. Partnering prospects will be assessed at that time, Inex said.

The company's stock (TSE:IEX) closed Friday at C$1.35. *

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