Alnylam Pharmaceuticals this week released new preclinical data showing that its preclinical complement-mediated diseases drug ALN-CC5 could cut serum levels of its target protein by up to 98 percent in non-human primates.
The company also said that it expects to nominate a development candidate from the program in early 2014, with an investigational new drug application ready for filing in early 2015.
The complement system is involved in immunity as a protective mechanism for host defense, according to the company. Dysregulation of the system can create serious complications in a variety of diseases including paroxysmal nocturnal hemoglobinuria, atypical hemolytic-uremic syndrome, myasthenia gravis, and neuromyelitis optica.
Alnylam's drug targets complement component C5, which is primarily expressed in liver cells and whose loss is associated with an attenuated immune response against certain infections. It is designed to be delivered subcutaneously.
In non-human primate testing, multiple doses of ALN-CC5 at 2.5 mg/kg or 5.0 mg/kg led to "rapid and dose-dependent knockdown" of serum C5 of up to 97.8 percent, with mean knockdown at nadir of 97.5 percent at the top dose, Alnylam said.
"Knockdown of C5 was durable, with greater than 90 percent knockdown sustained for up to three weeks after the final dose," the company added. "Further, subcutaneous administration resulted in a consistent greater than 80 percent knockdown of C5 during the treatment period."
Multiple doses of ALN-CC5 also resulted in "robust and durable" inhibition of hemolytic activity, it noted.
At 5 mg/kg, an up to 94 percent inhibition of hemolytic activity was observed, with a mean nadir reduction of 92 percent. Inhibition of hemolytic activity was sustained for at least two weeks after the final dose, and was shown to be "highly correlated" with serum levels of C5.
The data were presented at the annual meeting of the American Society of Hematology.