NEW YORK (GenomeWeb) – While its primary focus remains on a class of novel cell membrane-disrupting antimicrobials, privately held Lakewood-Amedex is ramping up work on proprietary, orally delivered antisense molecules, with an eye to tackling influenza and, eventually, other viral diseases.
Doing so, however, will require more capital than the company has on hand. In June, it closed a $5.5 million Series C preferred stock offering, but this money was specifically earmarked for advancing its lead antimicrobial agent into clinical testing, Lakewood-Amedex President and CEO Steve Parkinson told Gene Silencing News.
As such, the company is actively working on another fundraise to generate cash that can be used to conduct the additional animal testing necessary to move its antisense flu drug into human testing, he said.
Called nanoRNAs, Lakewood-Amedex's antisense oligos are highly protonated and modified with blocking groups on their ends, features that the firm claims makes them stable, resistant to nucleases, and permits oral, intravenous, and pulmonary delivery.
According to a recently allowed US patent application, the molecules range in length from about seven to 75 nucleotides and contain "seven or more contiguous ribose groups linked by achiral 5' to 3' internucleoside phosphate linkages."
NanoRNAs were invented by Lakewood-Amedex co-founder and former Yale University researcher Rod Dale, who initially developed them as gene-silencing therapeutics. Unexpectedly, he discovered that the molecules' chemical structure imparted antimicrobial properties completely unrelated to any nucleotide-based mechanism and likely due to their ability to disrupt bacterial cell membranes, Parkinson said.
Dale, before his death in 2008, reduced nanoRNAs to single-nucleotide cores with all of the modifications that had been developed for antisense applications. Called bisphosphocins, these redesigned molecules became Lakewood-Amedex's top priority and the nanoRNA program was moved to the backburner.
But amid the ongoing Ebola virus outbreak in West Africa, along with a growing number of enterovirus infections in the US, Lakewood-Amedex sees new opportunities for its nanoRNAs and is hoping to restart work on the technology, initially in flu.
Should it be able to raise additional financing, the company hopes to run new animal studies that would build on previous in vivo experiments and provide proof-of-concept data that could lead to an industry partnership or licensing deal, Parkinson said.
Among those earlier studies is one published in 2007 by Dale and collaborators at the Chinese Academy of Sciences demonstrating that intravenously administered nanoRNAs targeting Foxo-1, a gene involved in muscle development and growth, could increase skeletal muscle mass in a mouse model of cancer cachexia.
The next year, the researchers reported data showing that nanoRNAs targeting myostatin, a negative regulator of myogenesis, could silence their target and significantly increase muscle growth in cachectic mice when delivered either orally, intravenously, or intraperitoneally. Notably, intravenous and oral delivery had the most pronounced effects.
But it is Dale's work on influenza that Lakewood-Amedex is hoping to take forward first. In 2008, he and his Chinese Academy of Science collaborators published a study describing the design of nanoRNAs against the H5N1 avian influenza virus and showing that the molecules, when delivered intranasally, could protect infected chickens from death at a rate of up to 87.5 percent.
Parkinson noted that the investigators also generated data showing that the nanoRNA approach could protect mice infected with H1N1 swine flu. Preparations to have these findings published were never completed due to Dale's death, he added.
As it stands now, Lakewood-Amedex is targeting a Phase I study of its nanoRNAs in seasonal influenza for the first half of 2015. Whether that will be done alone or in conjunction with a partner has not yet been decided, and will likely depend on how much money the company can secure in its next financing round.
But "if we can show proof of concept in influenza and with the oral delivery technology, that opens the door to a multitude of opportunities," Parkinson said.