CAMBRIDGE, Mass. — Quiver Bioscience has received a multi-year grant from the National Institutes of Health to advance its lead Nav1.7-targeted antisense oligonucleotide therapy, QV-2421, through early clinical development for chronic neuropathic pain.
The award provides up to $9.3 million in direct funding and access to NIH-supported development resources, including chemistry, manufacturing and controls work and IND-enabling studies. Quiver said the total potential development support is approximately $20 million, including preclinical activities and an initial clinical trial, pending achievement of program milestones.
The grant, known as UG3NS146009, was awarded by the National Institute of Neurological Disorders and Stroke through the NIH Helping to End Addiction Long-term Initiative. The NIH HEAL Initiative was launched in 2018 to support research aimed at addressing the opioid crisis and improving pain management, including development of evidence-based, non-addictive treatments for chronic pain.
Quiver is developing QV-2421 as a potential non-opioid therapy targeting Nav1.7, a voltage-gated sodium channel linked to pain transmission. The company said the therapy is designed to reduce Nav1.7 expression in sensory neurons, with the goal of providing sustained and targeted pain relief without the addiction risks associated with opioid therapies.
Chronic neuropathic pain affects an estimated 7% to 10% of the global population and is often difficult to treat. Patients can experience burning, shooting and stabbing pain that disrupts sleep, mental health and quality of life. Current first-line therapies are effective in fewer than half of patients, while opioid-based treatments carry risks of dependence and adverse effects.
Quiver said Nav1.7 has long been viewed as one of the most promising pain targets because of strong human genetic evidence. People born without functional Nav1.7 are insensitive to pain, while gain-of-function mutations in the channel are linked to erythromelalgia and small fiber neuropathy. However, previous attempts to block Nav1.7 with small-molecule drugs have faced challenges involving selectivity, target engagement and tolerability.
“Chronic pain patients are profoundly underserved, and the limitations of small molecules have left one of the field’s most validated and compelling targets largely untapped. We believe our precision oligo-based approach to Nav1.7 can change that, offering a path to effective pain treatment for broad patient populations,” said Graham Dempsey, co-Founder and CEO of Quiver Bioscience.
Quiver plans to use its CNS drug discovery platform, which combines all-optical electrophysiology, patient-derived iPSC sensory neuron models and machine learning-guided antisense oligonucleotide design, to optimize QV-2421 and move the program toward clinical development.
The program also includes a collaboration with Dr. Charles Berde, MD, PhD, Sara Page Mayo Chair in Pediatric Pain Medicine in the Department of Anesthesiology, Critical Care and Pain Medicine at Boston Children’s Hospital and Professor of Anesthesia at Harvard Medical School. Berde is co-principal investigator of the award and will help support a Phase Ib trial in patients with erythromelalgia, an inherited chronic pain disorder.
“Support from the NIH HEAL Initiative provides an important opportunity to advance a non-opioid therapeutic strategy for chronic pain. By combining machine learning–guided ASO design with human iPSC-derived sensory neuron models and all-optical electrophysiology, we aim to precisely modulate Nav1.7 and translate strong human genetics into a viable therapy. We are excited to work with NIH to advance QV-2421 toward the clinic and ultimately bring new options to patients suffering from debilitating neuropathic pain,” said Hongkang Zhang, VP, Head of Pain Therapeutics Research at Quiver Bioscience and Principal Investigator of the award.
