RNAi startup Arcturus Therapeutics this week named transthyretin-mediated amyloidosis as the first indication to be added to its pipeline.
The disease is caused by mutations in the TTR gene, which triggers accumulation of abnormal amyloid proteins in the body. Notably, Alnylam Pharmaceuticals has been developing its own drugs for the disease, with an intravenously delivered one in phase III testing and a subcutaneously administered one in phase II.
Arcturus, however, uses proprietary siRNA-modification and drug-delivery technologies. Specifically, the company is developing drugs that incorporate unlocked nucleobase analog modifications — a technology acquired from Marina Biotech — and novel lipid nanoparticle carriers.
Arcturus said that in non-human primate testing, its UNA molecules treatment led to a greater than 75 percent knockdown of serum levels of the TTR protein after 10 days at a dose of 0.3 mg/kg. The effect, it added, lasted over three weeks with no adverse events associated with the delivery vehicles.
Rat toxicology studies, meanwhile, showed no incidence of adverse effects associated with multiple doses of Arcturus' RNAi compound, which was administered intravenously three times at 10 mg/kg over 15 days.
"Serum levels of the alanine aminotransferase and aspartate aminotransferase were determined after intravenous administration and no changes in these liver enzymes were observed," the firm said.
Arcturus CSO and COO Pad Chivukula said that the company expects to select a clinical candidate this year and enter phase I testing by early 2015, in line with previous guidance.