RNA interference, or RNAi, is a cellular mechanism that can be used to turn off the production of a protein. In the case of an RNAi directed against influenza, the target is one or more proteins critical for the virus' replication.
By turning off the production of such proteins, the spread of infection is prevented or slowed. Nastech's RNAi research and development programs seek to develop safe and effective therapeutics by identifying key protein targets, designing the RNAi that will turn those proteins off, and developing a formulation for the systemic delivery of this potential new class of therapeutics.
In connection with this new program, Nastech also announced the acquisition of the RNAi intellectual property estate and other RNAi technologies of Galenea. Financial terms of the transaction were not disclosed.
Galenea's lead RNAi product, G00101, has demonstrated efficacy against multiple influenza strains, including avian flu strains (H5N1) in animals. Nastech expects to work closely with the NIH, CDC and FDA to accelerate G00101 development given the urgent need for influenza therapeutics.
G00101 represents a first-in-class approach to fight influenza and is one of the most advanced anti-influenza compounds based on the recently discovered cellular mechanism known as small-interfering ribonucleic acid (siRNA). It is currently administered by inhalation to maximize delivery to the lung epithelium.
The product is designed for ease of use by patients and for long-term stability, essential for stockpiling the product for rapid mobilization during a flu epidemic. G00101 works by preventing viral replication and transcription in the airway epithelium. In vitro and in vivo studies have shown that these RNAi sequences provide broad-spectrum influenza protection and have reduced potential of drug resistance.
"This combination of Nastech's proprietary RNAi therapeutics delivery technologies with the intellectual property and technology developed by Galenea and MIT advances Nastech's position in developing innovative RNAi therapeutics," said Steven Quay, chairman, president and CEO of Nastech.
"The RNAi therapeutics program targeting the influenza virus is a high priority for Nastech as we believe it may offer an effective treatment for a future influenza pandemic, which is an urgent global concern. This program complements Nastech's current TNF-alpha RNAi program targeting inflammation, since a consequence of influenza infection can be life-threatening respiratory and systemic inflammation," he added.
The intellectual property acquired from Galenea includes patent applications licensed from MIT that have early priority dates in the antiviral RNAi field. Nastech also acquired Galenea's research and intellectual property relating to pulmonary drug delivery technologies.
Additionally, Nastech assumes Galenea's pending grant applications from the National Institute of Allergy and Infectious Diseases, a division of the National Institutes of Health, and the Department of Defense to support the development of RNAi-based antiviral drugs.
"It is anticipated that Nastech's RNAi delivery technology combined with the MIT intellectual property and the Galenea RNAi technology will provide a superior strategy to significantly speed the development of these promising new approaches for treating respiratory diseases, including influenza," said Jianzhu Chen, professor of Immunology at MIT and developer of the acquired RNAi antiviral technology, who will become a consultant to Nastech.
"The development of RNAi therapeutics targeting sequences that are highly conserved across all flu genomes, including avian and others having pandemic potential, represents a novel approach to the development of new therapies against influenza viruses."
According to the World Health Organization (WHO), in a typical year, influenza infects 5-15 per cent of the world's population, resulting in 250,000 to 500,000 deaths. The WHO and the Centers for Disease Control and Prevention are concerned about the potential for a major global pandemic such as the 1918 "Spanish flu" in which up to 50 million people may have died worldwide.
Pandemic flu emerges from a sudden change in the influenza virus that results in a new flu strain, against which there is no immunity. Vaccines currently represent the mainstay of flu prevention, but vaccines have two key limitations. First, they are developed against individual, known strains of flu and therefore may not be effective against new flu strains.
Second, vaccines are produced using a lengthy process requiring incubation in chicken eggs, thus vaccine against a new flu strain will take months or years to stockpile. Antiviral medications approved to treat influenza have the potential drawback that influenza virus strains can become resistant to one or more of these medications.
The potential advantage of RNAi antiviral therapeutics is that RNAi can be targeted against the so-called "conserved region" of the influenza virus. This means that an RNAi therapeutic would be expected to be effective against all strains of flu, whether new or old.
Therefore stockpiling of an effective RNAi treatment is possible in advance of a global influenza pandemic. In addition to a potential role in a pandemic flu outbreak, RNAi therapeutics could serve as a treatment for the more common seasonal flu that as noted above can result in hospitalisation and death.