J004 ALN-HTT02, a novel C16-sirna conjugate for HTT-lowering in the CNS

<h3></h3> Huntington’s disease (HD) is characterized by a progressive decline in behavioral, cognitive, and functional abilities, for which there are no available disease-modifying treatments. ALN-HTT02 is an investigational, intrathecally-administered, small interfering RNA (siRNA) that leverages recent advances in siRNA delivery to target both wild-type and all HD-associated isoforms of the HTT messenger RNA. Utilizing our C16-siRNA delivery platform, ALN-HTT02 is designed to potently and durably reduce HTT protein expression in neurons, and thereby has the potential to alter the course of HD progression. Here, we highlight the unique properties of the platform, share learnings regarding the tolerability of HTT-lowering in non-human primates, and outline an upcoming first-in-human Phase 1b study that will aim to characterize safety and tolerability of ALN-HTT02 in patients with HD.