When the severe acute respiratory syndrome coronavirus surfaced last year, researchers knew they needed a system for identifying new infectious agents in order to quickly develop therapeutics to counter them.
The threat of biowarfare only heightens that need, as does the rapid mutations of existent infectious strains.
Isis Pharmaceuticals Inc. believes its TIGER Biosensor provides the government with a broad-spectrum, rapid and accurate method for identifying infectious agents. Apparently, the government agrees.
The Defense Advanced Research Projects Agency (DARPA) granted Isis' Ibis Therapeutics program a two-year $19.5 million contract to further develop TIGER (Triangulation Identification Genetic Evaluation of Risks) to identify infectious agents in biological warfare attacks. The Ibis program is being conducted under a subcontract of San Diego-based Science Applications International Corp.
"The money is substantial," said Stanley Crooke, chairman and CEO of Carlsbad, Calif.-based Isis. "The added commitment of up to $19.5 million takes it up to $55 million that we've gotten to date [from the government], and we think it sets the stage for quite a bit of additional funding."
In addition to the DARPA funding, the Ibis program has received research funding from the Centers for Disease Control and Prevention, the U.S. Navy, the Federal Bureau of Investigation and the U.S. Army Medical Research Institute for Infectious Disease.
"We've been able to fund this program, essentially, entirely with funding from the government," Crooke told BioWorld Today. "That's been important to us because we have a good many things to invest in, such as our 11 antisense therapeutics."
Ibis scientists have used the TIGER biosensor to identify a variety of bacteria and viruses - some of them previously unknown - in several sample types, using a single test, without culturing. The program combines SAIC's advanced signal-processing capabilities with Ibis' expertise in microbial genome sequence analysis and advanced mass spectrometry technology.
"In a single diagnostic test we can rapidly and accurately identify essentially all infectious organisms contained in a sample," Crooke said in a conference call on Wednesday. "These organisms may be previously unknown, they may have been genetically altered, or they may be impossible to grow in the laboratory for identification through culturing."
Isis' Ibis program is focused on expanding on RNA-based drug discovery and development expertise. The goal is to create a platform technology that can identify a range of organisms in a single test and to develop small-molecule antibacterial and antiviral drugs that bind to RNA. The company's scientists integrate functional genomics, bioinformatics and RNA-focused chemistry programs with high-throughput, mass spectrometry-based screening methods.
"We believe that the TIGER system offers significant commercial opportunity for Isis for government applications such as infectious disease tracking and numerous commercial applications, such as clinical diagnostics and biological-products monitoring, including blood supply," Crooke said.
Identifying infectious organisms is a challenging task for several reasons, he added. For one, it's impossible to create an individual test for each one, as there are more than 1,000 organisms, including viral, bacterial, fungal and parasitic, that infect humans. Several of the organisms have multiple strain variants that mutate, making them moving targets. And many organisms have not been identified or are difficult to culture in a lab, not to mention that many of them are bioengineered.
Current technologies are not adequate, Crooke said.
"The recent SARS health crisis is one example of how inadequate current technologies are," he said. "Fortunately, the virus was cooperative and grew rapidly in culture so it took only months of intense work to identify the virus, while life was lost and economic costs mounted. It could have been much, much worse."
In addition to SARS, the TIGER Biosensor would be able to identify infectious agents such as the monkeypox virus, the West Nile virus or drug-resistant bacteria.
With continued funding of its Ibis program, Isis can concentrate its own resources on its lead antisense candidates.
The company's lead drug candidate, Affinitak, is in a Phase III program for non-small-cell lung cancer, and Alicaforsen is in Phase III for Crohn's disease. Alicaforsen, an antisense inhibitor of ICAM-1, also is being studied in a Phase II trial for ulcerative colitis. Other Phase II products include ISIS 14803 for hepatitis C, ISIS 104838 for rheumatoid arthritis and psoriasis, and ISIS 113715 for diabetes. Three other products - ISIS 301012, 112989 and 107248 - are in Phase I trials for cardiovascular, cancer and multiple sclerosis indications, respectively. Isis also is studying ISIS 23722 for cancer at the preclinical stage.
Phase III data of Affinitak in combination with carboplatin and paclitaxel showed no difference in overall survival - the primary endpoint - vs. chemotherapy alone. The drug, a selective inhibitor to protein kinase c-alpha expression, is being developed with Eli Lilly and Co., of Indianapolis, which is conducting a second Phase III trial evaluating Affinitak in combination with Gemzar and cisplatin.
Crooke said that Isis should receive data on eight clinical trials in the second half of this year, including data from the pivotal Alicaforsen trials in Crohn's disease and ulcerative colitis and from the second Phase III trial of Affinitak in lung cancer.
Isis has one antisense product on the market, Vitravene, to treat CMV retinitis in AIDS patients, which was approved in 1998.
The company has 1,350 issued patents, which cover its TIGER Biosensor, as well as its antisense technology.
The company's stock (NASDAQ:ISIS) rose 51 cents on Wednesday to close at $8.87.