Encoded Therapeutics Unveils Promising Preclinical Data for One-Time, Non-Opioid Gene Therapy Targeting Chronic Pain

Encoded Therapeutics has announced new preclinical data supporting the therapeutic potential of its AAV9-based gene therapy candidate for chronic pain, highlighting a breakthrough approach to treating one of the most pervasive and underserved neurological conditions. The data, presented at the 32nd Annual Congress of the European Society of Gene & Cell Therapy and the upcoming 19th Annual Pain Therapeutics Summit, demonstrate strong efficacy in non-human primate (NHP) and rodent models.

The therapy centers on the precise and durable knockdown of SCN9A (NaV1.7), a voltage-gated sodium channel that plays a key role in pain signaling. While NaV1.7 has long been recognized as a validated target for pain modulation, it has historically proven difficult to selectively inhibit. Encoded’s approach uses an AAV9-delivered microRNA (miRNA) construct to silence SCN9A expression in dorsal root ganglia (DRG) neurons—regions critical to pain transmission—while minimizing exposure to other organs such as the brain, heart, and liver.

In NHP models, a single intrathecal administration of low-dose AAV9 achieved 69% knockdown of SCN9A expression in lumbar DRG, surpassing efficacy thresholds previously established in rodent studies. Biodistribution analyses showed minimal off-target exposure, suggesting a favorable safety profile. Complementary studies in rats demonstrated durable analgesic effects in a chronic pain model, where just 40% knockdown of Scn9a was sufficient to produce lasting pain relief for at least eight weeks post-treatment.

The treatment was well-tolerated in both species, with no dose-limiting toxicities or adverse findings observed. These results provide a robust translational foundation for advancing a gene therapy-based solution for chronic pain—a condition currently managed with therapies that are often inadequate and carry substantial risk, including dependency and systemic side effects.

The novel candidate is a product of Encoded Therapeutics' proprietary vector engineering platform, which enables precise and lasting gene modulation in targeted tissues. Building on its platform success with ETX101, a clinical-stage program for Dravet syndrome, the company is expanding into other high-impact neurological disorders, including chronic pain, Angelman syndrome, and Alzheimer’s disease.

Encoded’s chronic pain program is on track for further development in 2026. The preclinical findings reinforce the company’s commitment to delivering one-time therapies that address root causes of neurological conditions, offering new hope for millions living with intractable pain.