PNM-CAP: A novel nerve cap to prevent painful neuroma formation in peripheral nerve injuries and amputations

2.1M people live with extremity amputation (EA), and >220,000 new EAs are performed annually in the US. Each EA transects on average 2.5 nerves, expanding the prevalence to >5M and the incidence to 565,000 nerves with the potential to develop painful neuroma, which occurs in up to 48% of lower extremity amputees. 54.7% of patients who undergo lower EA receive opioid analgesia and 44.6% seek prolonged postoperative opioid use - placing them at high risk for opioid use disorder (OUD) and/or overdose. Despite the existence of different solutions to prevent and/or treat neuroma following EA, these are associated with multiple shortcomings making them unable to satisfactorily resolve a significant unmet clinical need, as demonstrated by multiple statistics. Renerva, LLC has developed a nerve capping device (PNM-CAP) to prevent neuroma formation following extremity amputations. PNM-CAP is a terminally sterilized biodegradable device obtained from porcine peripheral nerves via proprietary chemical, mechanical, and physical processes. The device can be easily and rapidly secured to each nerve end during an EA procedure without specialized surgical training or procedural extension. PNM-CAP has an internal neuro-inhibitory matrix providing a resistive pathway that allows compartmentalized and limited sprouting and extending of axons from the amputated nerve into the device. During this process, the device degrades and remodels into a stable amputated nerve stump in which the internal axons have exhausted their intrinsic regenerative potential in close proximity (<6mm) to the original nerve ending leading to long-term neuroma prevention. Published results in a rat model have corroborated these mechanisms of action showing complete interruption of nerve growth following peripheral nerve amputation without any evidence of neuroma. Multiple independent animal studies with an external partner have further confirmed these results. The present proposal seeks to complete vital official tests required for regulatory submission for US market clearance of PNM-CAP. These include two short-term in vivo safety studies and a long-term in vivo efficacy study under good laboratory practice controls in rodent models of neurectomy and neuroma formation and pain, respectively. If successful, this Phase I project will critically abate the technical risk associated with PNM-CAP opening the door to a Phase II (and external investment), which will support the completion of the remaining resource-intensive tests required for bring PNM-CAP to the clinic. As a result, this project has the potential to reduce the clinical rate of development of neuroma following EA, the associated dependence on pharmacological pain management, and the incidence of opioid use disorder.