Alios BioPharma Inc. is looking to tackle the shortcomings of antiviral drugs by increasing the potency of interferon and creating a new class of broad-spectrum antivirals.
The South San Francisco-based company was founded late last year by Lawrence Blatt, who gained experience in virology and immunology through previous positions with Amgen Inc. and InterMune Inc., among others. At Alios, Blatt and his team developed a lead program around glycosylated interferon, an approach he said "can have the same effect as pegylation without giving up the biological potency."
Treatment with pegylated interferon plus ribavirin is the standard of care for hepatitis C viral infection. That approach often comes under fire for its 40 percent to 50 percent cure rate, but Blatt pointed out that it is "the only example of a virus being cured." If the cure rate was applied as the standard for HIV drugs, none of them would work, he added.
Interferon's use in HCV is not likely to decrease any time soon. Most of the new protease and polymerase inhibitors in development are designed to be given in combination with the old standard. But the pegylation that makes interferon last longer also decreases its potency. In preclinical studies, Alios' glycosylated Type I interferon, Glycoferon, demonstrated 1,000-fold greater potency in vitro than pegylated interferon-alpha.
While Alios isn't the only company seeking to improve on pegylated interferon, Blatt said most of the others are focusing on less frequent delivery and do not address the potency issue. One exception is San Diego-based Ambrx Inc., which has demonstrated improved activity over pegylated interferon alpha in preclinical studies with its approach of using pegylated non-naturally occurring, chemically unique amino acids.
Alios' Glycoferon is about nine to 12 months from entering the clinic, Blatt said. Behind it in the pipeline are glycosylated interferons for cancer and multiple sclerosis. The cancer product, Oncoferon, is a glycosylated version of interferon alpha-1 that is long acting and might offer decreased toxicity due to the interferon species chosen, Blatt told BioWorld Today. The MS product, Beta-Gly, is a glycosylated version of interferon beta.
Earlier this month, Alios expanded its pipeline beyond the glycosylation program by licensing a portfolio of small-molecule RNase L activators from the Cleveland Clinic. RNase L is an enzyme that is present but inactive in most human cells. It becomes activated during viral infections and works downstream of interferon to degrade viral RNA and prevent viral replication. Preclinical results, published by Robert Silverman of the Lerner Research Institute in Cleveland in a June issue of The Proceedings of the National Academy of Sciences, showed that two RNase L activators inhibited the growth of five different types of RNA viruses, yet had no activity in cells where RNase L had been deleted. (See BioWorld Today, June 26, 2007.)
Blatt said the small molecules also have demonstrated activity against DNA viruses and retroviruses, all without causing cytotoxicity. Those properties indicate broad-spectrum antiviral potential - a field that has proven far more difficult than the creation of broad-spectrum antibiotics. Interferons are one of the few broad-spectrum antivirals around, but Blatt said the downstream action of RNase L activators should allow for better efficacy in treating chronic viruses that often shut off interferon production.
Broad-spectrum antivirals potentially could be used to treat patients infected with unidentified viruses, whether it's a single patient who arrives in an emergency room with strange viral symptoms or an incident involving many patients affected by an unknown pathogen, such as in biowarfare. Another potential use could be in the treatment of fast-spreading new viruses such as avian influenza or the virus that causes severe acute respiratory syndrome (SARS), for which treatments have not yet been developed.
Alios's deal with the Cleveland Clinic gives the company exclusive worldwide rights to the RNase L activator technology, patents and preclinical compounds for use in viral diseases and cancer as well as all other human, veterinary and agricultural applications. In exchange, Alios paid an undisclosed up-front fee and will make additional development, regulatory and commercial milestone payments, as well as royalty payments. Alios also will sponsor ongoing research at the Cleveland Clinic for two years.
Blatt said Alios plans to develop the RNase L activators as complementary approaches to existing treatments for viral diseases and cancer. A monotherapy approach is not likely to work in either field, he added.
For now, Alios has about 10 employees and is "more or less virtual," Blatt said. The company raised initial funding from angel investors but is now in the process of raising a Series A round. In the future, Blatt said Alios will "absolutely" look for partners for its programs.