Age-related macular degeneration has been the disease du jour for a number of RNAi drug developers — including Alnylam Pharmaceuticals, Sirna Therapeutics, and Acuity Pharmaceuticals — both because treatments can easily be administered directly to the eye, and because the disease has a well-validated therapeutic target in vascular endothelial growth factor.
Now Quark Biotech has entered the field, announcing last week that it, too, will pursue development of a directly delivered RNAi-based treatment for AMD. But Quark is coming at the disease from a different angle by targeting the gene RTP801 rather than the VEGF pathway.
RTP801 “is a critical gene in three different phenotypes,” Daniel Zurr, CEO of Quark, told RNAi News this week. “One is neovascularization, the other is permeability of vasculature, and the third is apoptosis.”
Given this, the company sees potential for compounds silencing the gene in not only AMD, which is characterized by abnormal blood vessel growth in the macula, but also diabetic retinopathy and retinopathy of prematurity.
Zurr said that Quark discovered RTP801 in the 1990s, but until RNAi came onto the scene there was no viable way to target the gene therapeutically.
“We had the gene years ago … and we went the classical way to ascertain the function of the gene and the pathway,” he said, adding that the company plans to publish details about the gene’s mechanism of action soon. It turned out that “this particular target is not amenable for the development of small molecules … but we were lucky to find something very active [in an] siRNA.”
Thus far, Quark has tested an RTP801-targeting siRNA in rodents and monkeys, with “encouraging” results, Zurr said. These results, along with data from an RTP801 knockout animal the company developed, are expected to be presented at the second annual Ocular Angiogenesis conference in Cambridge, Mass., on March 24 and 25.
Zurr added that the siRNA sequence the company expects to develop as a therapeutic is the same one used in animal experiments, indicating that “this gene is very conserved.” He added that the siRNA was developed through an arrangement with Atugen, which provided the technology for chemically modifying the siRNA.
Peter Buckel, CEO of Atugen, told RNAi News this week that the companies also signed an agreement about a month ago to work together on siRNAs targeting RTP801.
According to Buckel, the partnership made sense for the companies because each had independently struck upon the therapeutic potential of the gene — Quark making its discovery in ocular diseases and Atugen in cancer.
Both companies have filed for patents on the use of RNAi molecules against the gene in their respective disease areas, Buckel said, and by partnering “we have a very strong [IP] position together.”
Buckel said that the companies’ deal is “a 50/50 collaboration” for both indications, and each partner can participate in the development efforts of the other. He added that the deal includes cost and revenue-sharing options, but declined to comment on whether the arrangement also includes the possibility of joint commercialization of potential products.
Zurr declined to comment on the Atugen collaboration, noting that additional details would be released when the collaboration is officially made public in an upcoming press release.
Buckel said Atugen is expecting to file an investigational new drug application to begin clinical trials on an RNAi-based drug targeting RTP801 for cancer next year. Zurr said that Quark expects to file an IND on an AMD treatment at the end of this year.