By Frances Bishopp

In 1989, Oligos Etc./Oligo Therapeutics Inc. (OE/OT) was founded on a premise that was and still is fairly unusual in the biotechnology arena: build a profitable business that will finance not only the company, but its research programs, and do it without investor money.

Today, the company, which was profitable in its first year of selling short RNA and DNA sequences to clients for research and clinical trials, is looking for collaborators to finance the next step of its research program (clinical trials) that focuses on creating antisense oligonucleotides that inhibit pathogenic bacteria.

In fact, over the last eight years, the privately held company, which has a production facility in Wilsonville, Ore., and a business office in Newton, Conn., has managed to accomplish its goals and currently is talking to the FDA about commencing Phase I trials in the not-so-distant future.

"We wanted to begin a company that had a positive cash flow," said Vice President Amy Arrow.

In 1995, OE/OT completed a 17,000-square-foot manufacturing facility, which, she said, was paid for by putting profits back into the company. "It's been a long-term plan," she said, "based on the idea of making money and putting it back into the company."

In the research arena, OE/OT is working on the development of an oligonucleotide-based class of antibiotics effective against the rapidly growing population of antibiotic-resistant bacteria. Antibiotic-resistant bacteria have become a problem in the world today, Arrow told BioWorld Today, with more and more people dying daily from bacterial infections that could have been cured only a decade ago.

OE/OT is waging the war against bugs that fight back with oligonucleotide antibiotics, or "nubiotics." An oligos is a short piece of synthetic DNA. OE/OT looks at particular genes for a particular disease and targets antisense oligos to that gene to test the bacteria's ability to survive by shutting down the gene product.

"We have developed a new class of antibiotics that work against drug-resistant bacteria," Arrow said. "It's unique in that not only is it a new class, but the whole philosophy behind the development of the antibiotic is different."

OE/OT's technology, for which it has several patents, is based on synthesizing oligos which have both specific and broad antibacterial activities. In vitro tests on more than 20 bacterial strains have shown the oligos' effectiveness against bacteria, including antibiotic-resistant organisms.

"Most of the different classes of antibiotics are derived from microbial sources," Arrow said. "What we have done is come up with a completely synthetic, rationally defined and rationally designed approach to an antibiotic, so there is no counterpart in nature.

"The advantages of this approach," she continued, "is you are less likely to have inherent drug resistance to it because there is no organism that is already resistant to it, since it is not something that naturally occurs."

If the bacteria were to develop resistance to a particular synthetic oligo, Arrow said, that oligo can be changed. "It's a very flexible type of product," she added.

Preliminary animal studies have supported these results. "In animals, we have looked at the ability to function against a gram-positive organism, as well as a gram-negative organism, where we are comparing to placebo-treated controls, so what we are following is a clinical sepsis model, where mortality is an endpoint," she said. OE/OT has been successful in all of these areas, she said.

Oligos, she said, have been used primarily for chronic illness, such as Crohn's disease, HIV or cancer. Oligos, used in a situation of acute infection, appear to work very well, she said.

"Most of the antibiotics out there are shorter acting and less long-lived," Arrow said. "We have found that using oligos as antibiotics works very well against every organism we have tested them against."

In terms of its bread and butter--the making of oligos --Arrow is adamant about the quality of the product. "It helps to do your own research," Arrow said, "because you know what kind of quality you need. We won't sell what we wouldn't use for ourselves." *