Quiver Bioscience, a Cambridge, Massachusetts-based biotech company, has received a USD 1.99 million NIH UG3 award from the National Institute of Neurological Disorders and Stroke (NINDS) to advance an antisense oligonucleotide (ASO) program targeting Nav1.7 for chronic neuropathic pain, with a planned trajectory toward Phase I clinical testing.
The grant, recorded in NIH RePORTER as 1UG3NS146009-01, funds development of QV-2421, Quiver Bioscience's lead ASO candidate designed to knock down mRNA encoding the voltage-gated sodium channel Nav1.7, which is highly expressed in dorsal root ganglion neurons and has strong human genetic validation as a mediator of pain transmission. Loss-of-function mutations in the SCN9A gene, which encodes Nav1.7, produce congenital insensitivity to pain in humans — a genetic precedent that underpins the therapeutic rationale for channel knockdown rather than blockade.
The UG3 phase will focus on lead optimization, in vivo tolerability evaluation, and translational biomarker development. Quiver is collaborating with Boston Children's Hospital to validate QV-2421's functional activity in sensory neurons derived from patients with erythromelalgia and small fiber neuropathy, two rare neuropathic pain conditions with limited treatment options. The company said intrathecal delivery is intended to achieve selective Nav1.7 knockdown in dorsal root ganglion tissue while minimizing systemic and autonomic exposure.
Quiver's approach combines three proprietary technologies: all-optical electrophysiology for high-throughput readout of neuronal excitability, human iPSC-derived sensory neuron models incorporating patient genetics, and a machine learning-guided ASO design platform. The company said QV-2421 was identified through in silico prediction and confirmed in primary dorsal root ganglion neurons from multiple species, with an acceptable central nervous system tolerability profile in early in vivo testing.
The award runs through March 2028. If UG3 milestones are met — including selection of an optimized ASO candidate with acceptable tolerability and non-human primate pharmacokinetic and pharmacodynamic data — the program is structured to advance into a UH3 phase covering dose-range finding toxicology, large-scale manufacturing, IND-enabling studies, and initiation of a Phase I trial in young adult patients with erythromelalgia.